Insecticidal compounds

ABSTRACT

A compound of formula (I): 
                         
wherein A 1 , A 2 , A 3 , A 4 , A 5 , G 1 , R 1 , R 2 , R 3  and R 4  are as defined in claim  1 ; or a salt or N-oxide thereof.
 
     Furthermore, the present invention relates to processes and intermediates for preparing compounds of formula (I), to insecticidal, acaricidal, nematicidal and molluscicidal compositions comprising them and to methods of using them to combat and control insect, acarine, nematode and mollusc pests.

This application is continuation of U.S. application Ser. No.13/145,689, filed Jun. 21, 2011, which is a 371 of InternationalApplication No. PCT/EP2010/050358, filed Jan. 13, 2010, which claimspriority to 127/DELNP/2009, filed Jan. 22, 2009, GB 0910767.3, filedJun. 22, 2009, and PCT/EP2009/059563, filed Jul. 24, 2009, the contentsof which are incorporated herein by reference.

The present invention relates to certain benzamide isoxazolines, toprocesses and intermediates for preparing them, to insecticidal,acaricidal, nematicidal and molluscicidal compositions comprising themand to methods of using them to combat and control insect, acarine,nematode and mollusc pests.

Certain bicyclic isoxazoline derivatives with insecticidal propertiesare disclosed, for example, in WO 2007/079162, WO 2008/154528 and WO2009/002809.

It has now surprisingly been found that certain isoxazoline-substitutedbicyclic heteroaromatic compounds have insecticidal properties.

The present invention therefore provides a compound of formula (I)

whereinA¹, A² and A³ are independently C—R⁵, nitrogen, N—R⁶, oxygen or sulfur,provided that two of A¹, A² or A³ are C—R⁵ or nitrogen and that one ofA¹, A² or A³ is N—R⁶, oxygen or sulfur;A⁴ and A⁵ are independently C—R⁵ or nitrogen;G¹ is oxygen or sulfur;R¹ is hydrogen, C₁-C₈alkyl, C₁-C₈alkylcarbonyl-, orC₁-C₈alkoxycarbonyl-;R² is C₁-C₈alkyl or C₁-C₈alkyl substituted by one to five R⁷,C₃-C₁₀cycloalkyl or C₃-C₁₀cycloalkyl substituted by one to five R⁸,aryl-C₁-C₄alkylene- or aryl-C₁-C₄alkylene- wherein the aryl moiety issubstituted by one to five R⁹, heterocyclyl-C₁-C₄alkylene- orheterocyclyl-C₁-C₄alkylene- wherein the heterocyclyl moiety issubstituted by one to five R⁹, aryl or aryl substituted by one to fiveR⁹, heterocyclyl or heterocyclyl substituted by one to five R⁹,C₁-C₈alkylaminocarbonyl-C₁-C₄ alkylene,C₁-C₈haloalkylaminocarbonyl-C₁-C₄ alkylene, orC₃-C₈cycloalkyl-aminocarbonyl-C₁-C₄ alkylene;R³ is C₁-C₈haloalkyl;R⁴ is aryl or aryl substituted by one to five R¹⁰, or heteroaryl orheteroaryl substituted by one to five R¹⁰;each R⁵ is independently hydrogen, halogen, cyano, nitro, C₁-C₈alkyl,C₁-C₈haloalkyl, C₁-C₈alkoxy, C₁-C₈haloalkoxy, C₁-C₈alkylthio-,C₁-C₈haloalkylthio-, C₁-C₈alkylsulfinyl-, C₁-C₈haloalkylsulfinyl-,C₁-C₈alkylsulfonyl-, or C₁-C₈haloalkylsulfonyl-;each R⁶ is independently hydrogen or C₁-C₈alkyl;each R⁷ is independently halogen, cyano, nitro, hydroxy, C₁-C₈alkoxy,C₁-C₈haloalkoxy, mercapto, C₁-C₈alkylthio-, C₁-C₈haloalkylthio-;C₁-C₈alkylsulfinyl-, C₁-C₈haloalkylsulfinyl-, C₁-C₈alkylsulfonyl-, orC₁-C₈haloalkylsulfonyl-;each R⁸ is independently halogen or C₁-C₈alkyl;each R⁹ and R¹⁰ is independently halogen, cyano, nitro, C₁-C₈alkyl,C₁-C₈haloalkyl, C₂-C₈alkenyl, C₂-C₈haloalkenyl, C₂-C₈alkynyl,C₂-C₈haloalkynyl, hydroxy, C₁-C₈alkoxy, C₁-C₈haloalkoxy, mercapto,C₁-C₈alkylthio-, C₁-C₈haloalkylthio-, C₁-C₈alkylsulfinyl-,C₁-C₈haloalkylsulfinyl-, C₁-C₈alkylsulfonyl-, C₁-C₈haloalkylsulfonyl-,C₁-C₈alkylcarbonyl-, C₁-C₈alkoxycarbonyl-, aryl or aryl substituted byone to five R¹¹, or heterocyclyl or heterocyclyl substituted by one tofive R¹¹; andeach R¹¹ is independently halogen, cyano, nitro, C₁-C₄alkyl,C₁-C₄haloalkyl, C₁-C₄alkoxy, or C₁-C₄haloalkoxy; or a salt or N-oxidethereof;provided that -A¹-A²-A³- is not —O—(CR⁵)═N—, —S—(CR⁵)═N—, N═(CR⁵)—O— or—N═(CR⁵)—S— irrespective of the values for A⁴ and A⁵, andprovided that -A¹-A²-A³- is not —(CR⁵)═(CR⁵)—O—, —O—(CR⁵)═(CR⁵)—,—(CR⁵)═(CR⁵)—S—, —S—(CR⁵)═(CR⁵)—, —(CR⁵)═(CR⁵)—(NR⁶)—,—(NR⁶)—(CR⁵)═(CR⁵)—, —(CR⁵)═N—(NR⁶)— and —(NR⁶)—N═(CR⁵)— when A⁴ and A⁵are both C—R⁵.

The compounds of formula (I) may exist in different geometric or opticalisomers or tautomeric forms. This invention covers all such isomers andtautomers and mixtures thereof in all proportions as well as isotopicforms such as deuterated compounds.

The compounds of the invention may contain one or more asymmetric carbonatoms, for example, at the —CR³R⁴— group, and may exist as enantiomers(or as pairs of diastereo-isomers) or as mixtures of such.

Alkyl groups (either alone or as part of a larger group, such as alkoxy,alkylthio-, alkylsulfinyl-, alkylsulfonyl-, alkylcarbonyl-, oralkoxycarbonyl-) can be in the form of a straight or branched chain andare, for example, methyl, ethyl, propyl, prop-2-yl, butyl, but-2-yl,2-methyl-prop-1-yl or 2-methyl-prop-2-yl. The alkyl groups arepreferably C₁-C₆, more preferably C₁-C₄, most preferably C₁-C₃ alkylgroups. Where an alkyl moiety is said to be substituted, the alkylmoiety is preferably substituted by one to four substituents, mostpreferably by one to three substituents.

Alkylene groups can be in the form of a straight or branched chain andare, for example, —CH₂—, —CH₂—CH₂—, —CH(CH₃)—, —CH₂—CH₂—CH₂—,—CH(CH₃)—CH₂—, or —CH(CH₂CH₃)—. The alkylene groups are preferablyC₁-C₃, more preferably C₁-C₂, most preferably C₁ alkylene groups.

Alkenyl groups can be in the form of straight or branched chains, andcan be, where appropriate, of either the (E)- or (Z)-configuration.Examples are vinyl and allyl. The alkenyl groups are preferably C₂-C₆,more preferably C₂-C₄, most preferably C₂-C₃ alkenyl groups.

Alkynyl groups can be in the form of straight or branched chains.Examples are ethynyl and propargyl. The alkynyl groups are preferablyC₂-C₆, more preferably C₂-C₄, most preferably C₂-C₃ alkynyl groups.

Halogen is fluorine, chlorine, bromine or iodine.

Haloalkyl groups (either alone or as part of a larger group, such ashaloalkoxy, haloalkylthio-, haloalkylsulfinyl- or haloalkylsulfonyl-)are alkyl groups which are substituted by one or more of the same ordifferent halogen atoms and are, for example, difluoromethyl,trifluoromethyl, chlorodifluoromethyl or 2,2,2-trifluoro-ethyl.

Haloalkenyl groups are alkenyl groups which are substituted by one ormore of the same or different halogen atoms and are, for example,2,2-difluoro-vinyl or 1,2-dichloro-2-fluoro-vinyl.

Haloalkynyl groups are alkynyl groups which are substituted by one ormore of the same or different halogen atoms and are, for example,1-chloro-prop-2-ynyl.

Cycloalkyl groups can be in mono- or bi-cyclic form and are, forexample, cyclopropyl, cyclobutyl, cyclohexyl andbicyclo[2.2.1]heptan-2-yl. The cycloalkyl groups are preferably C₃-C₈,more preferably C₃-C₆ cycloalkyl groups. Where a cycloalkyl moiety issaid to be substituted, the cycloalkyl moiety is preferably substitutedby one to four substituents, most preferably by one to threesubstituents.

Aryl groups (either alone or as part of a larger group, such asaryl-alkylene-) are aromatic ring systems which can be in mono-, bi- ortricyclic form. Examples of such rings include phenyl, naphthyl,anthracenyl, indenyl or phenanthrenyl. Preferred aryl groups are phenyland naphthyl, phenyl being most preferred. Where an aryl moiety is saidto be substituted, the aryl moiety is preferably substituted by one tofour substituents, most preferably by one to three substituents.

Heteroaryl groups (either alone or as part of a larger group, such asheteroaryl-alkylene-) are aromatic ring system containing at least oneheteroatom and consisting either of a single ring or of two or morefused rings. Preferably, single rings will contain up to threeheteroatoms and bicyclic systems up to four heteroatoms which willpreferably be chosen from nitrogen, oxygen and sulfur. Examples ofmonocyclic groups include pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl,pyrrolyl, pyrazolyl, imidazolyl, triazolyl, furanyl, thiophenyl,oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl andthiadiazolyl. Examples of bicyclic groups include quinolinyl,cinnolinyl, quinoxalinyl, indolyl, indazolyl, benzimidazolyl,benzothiophenyl and benzothiazolyl. Monocyclic heteroaryl groups arepreferred, pyridyl being most preferred. Where a heteroaryl moiety issaid to be substituted, the heteroaryl moiety is preferably substitutedby one to four substituents, most preferably by one to threesubstituents.

Heterocyclyl groups (either alone or as part of a larger group, such asheterocyclyl-alkylene-) are defined to include heteroaryl groups and inaddition their unsaturated or partially unsaturated analogues. Examplesof monocyclic groups include thietanyl, pyrrolidinyl, tetrahydrofuranyl,[1,3]dioxolanyl, piperidinyl, piperazinyl, [1,4]dioxanyl, andmorpholinyl or their oxidised versions such as 1-oxo-thietanyl and1,1-dioxo-thietanyl. Examples of bicyclic groups include2,3-dihydro-benzofuranyl, benzo[1,3]dioxolanyl, and2,3-dihydro-benzo[1,4]dioxinyl. Where a heterocyclyl moiety is said tobe substituted, the heterocyclyl moiety is preferably substituted by oneto four substituents, most preferably by one to three substituents.

Preferred values of A¹, A², A³, A⁴, A⁵, G¹, R¹, R², R³, R⁴, R⁵, R⁶, R⁷,R⁸, R⁹, R¹⁰ and R¹¹ are, in any combination, as set out below.

For the avoidance of doubt, the ring formed by A¹, A² and A³ is anaromatic ring.

Preferably A¹ is nitrogen or N—R⁶, most preferably nitrogen or N—CH₃.

Preferably A² is C—R⁵, N—R⁶, nitrogen or sulfur, more preferably A² isC—R⁵, nitrogen or sulfur, most preferably nitrogen or sulfur.

Preferably A³ is nitrogen or N—R⁶, most preferably nitrogen or N—CH₃.

In one embodiment A¹ and A³ are nitrogen or N—R⁶ and A² is C—R⁵, N—R⁶,nitrogen or sulfur, more preferably A¹ and A³ are nitrogen or N—R⁶ andA² is N—R⁶, nitrogen or sulfur, more preferably A¹ and A³ are nitrogenand A² is N—R⁶ or sulfur. For example, -A¹-A²-A³- may be selected from═N—S—N═, —N═C(R⁵)—N(R⁶)—, —N(R⁶)—C(R⁵)═N—, ═N—N(R⁶)—N═, —N═N—N(R⁶)— and—N(R⁶)—N═N—, more preferably ═N—S—N═, —N═C(R⁵)—N(R⁶)—, ═N—N(R⁶)—N═, and—N═N—N(R⁶)—, more preferably ═N—S—N═, ═N—N(R⁶)—N═, and —N═N—N(R⁶)—, mostpreferably ═N—S—N═. In one embodiment two of A¹, A² and A³ are nitrogenand the other of A¹, A² and A³ is N—R⁶, oxygen or sulfur, morepreferably two of A¹, A² and A³ are nitrogen and the other of A¹, A² andA³ is N—R⁶ or sulfur. For example, -A¹-A²-A³- may be selected from═N—S—N═, —S—N═N—, —N═N—S—, ═N—N(R⁶)—N═, —N═N—N(R⁶)— and —N(R⁶)—N═N—, inparticular from ═N—S—N═, —N═N—N(R⁶)— and ═N—N(R⁶)—N═. Preferably two ofA¹, A² and A³ are nitrogen and the other of A¹, A² and A³ is sulfur. Forexample, -A¹-A²-A³- may be selected from ═N—S—N═, —S—N═N—, and —N═N—S—.Most preferably -A¹-A²-A³- is ═N—S—N═.

Preferably A⁴ is C—R⁵, most preferably C—H or C—CH₃, in particular C—H.

Preferably A⁵ is C—R⁵, most preferably C—H.

For example, A⁴ and A⁵ may each independently be C—H or nitrogen, morepreferably A⁴ and A⁵ are both C—H.

Preferably G¹ is oxygen.

Preferably R¹ is hydrogen, methyl, ethyl, methylcarbonyl-, ormethoxycarbonyl-, more preferably hydrogen, methyl or ethyl, even morepreferably hydrogen or methyl, most preferably hydrogen.

Preferably R² is C₁-C₈alkyl or C₁-C₈alkyl substituted by one to five R⁷,C₃-C₁₀cycloalkyl or C₃-C₁₀cycloalkyl substituted by one to five R⁸,aryl-C₁-C₄alkylene- or aryl-C₁-C₄alkylene- wherein the aryl moiety issubstituted by one to five R⁹, heterocyclyl-C₁-C₄alkylene- orheterocyclyl-C₁-C₄alkylene- wherein the heterocyclyl moiety issubstituted by one to five R⁹, aryl or aryl substituted by one to fiveR⁹, heterocyclyl or heterocyclyl substituted by one to five R⁹,C₁-C₈alkylaminocarbonyl-C₁-C₄ alkylene,C₁-C₈haloalkylaminocarbonyl-C₁-C₄ alkylene, orC₃-C₈cycloalkyl-aminocarbonyl-C₁-C₄ alkylene, wherein each aryl group isa phenyl group and each heterocycle group is selected from pyridyl,pyridazinyl, pyrimidinyl, pyrazinyl, pyrrolyl, pyrazolyl, imidazolyl,triazolyl, furanyl, thiophenyl, oxazolyl, isoxazolyl, oxadiazolyl,thiazolyl, isothiazolyl, thiadiazolyl, quinolinyl, cinnolinyl,quinoxalinyl, indolyl, indazolyl, benzimidazolyl, benzothiophenyl,benzothiazolyl, oxetanyl, thietanyl, oxo-thietanyl, dioxo-thietanyl,pyrrolidinyl, tetrahydrofuranyl, [1,3]dioxolanyl, piperidinyl,piperazinyl, [1,4]dioxanyl, and morpholinyl, 2,3-dihydro-benzofuranyl,benzo[1,3]dioxolanyl, and 2,3-dihydro-benzo[1,4]dioxinyl.

Preferably R² is C₁-C₈alkyl or C₁-C₈alkyl substituted by one to five R⁷,C₃-C₁₀cycloalkyl or C₃-C₁₀cycloalkyl substituted by one to five R⁸,aryl-C₁-C₄alkylene- or aryl-C₁-C₄alkylene- wherein the aryl moiety issubstituted by one to five R⁹, heterocyclyl-C₁-C₄alkylene- orheterocyclyl-C₁-C₄alkylene- wherein the heterocyclyl moiety issubstituted by one to five R⁹, aryl or aryl substituted by one to fiveR⁹, heterocyclyl or heterocyclyl substituted by one to five R⁹,C₁-C₈alkylaminocarbonyl-C₁-C₄ alkylene,C₁-C₈haloalkylaminocarbonyl-C₁-C₄ alkylene, orC₃-C₈cycloalkyl-aminocarbonyl-C₁-C₄ alkylene, wherein each aryl group isa phenyl group and each heterocycle group is selected from pyridyl,pyrazolyl, benzimidazolyl, furanyl, thiazolyl, oxetanyl, thietanyl,oxo-thietanyl and dioxo-thietanyl.

Preferably R² is C₁-C₈alkyl or C₁-C₈alkyl substituted by one to five R⁷,C₃-C₁₀cycloalkyl or C₃-C₁₀cycloalkyl substituted by one to five R⁸,phenyl-C₁-C₄alkylene- or phenyl-C₁-C₄alkylene- wherein the phenyl moietyis substituted by one to five R⁹, pyridyl-C₁-C₄alkylene- orpyridyl-C₁-C₄alkylene- wherein the pyridyl moiety is substituted by oneto four R⁹, imidazolyl-C₁-C₄alkylene or imidazolyl-C₁-C₄alkylene whereinthe imidazolyl moiety is substituted by one to five R⁹, oxetanyl oroxetanyl substituted by one to five R⁹, thietanyl or thietanylsubstituted by one to five R⁹, oxo-thietanyl or oxo-thietanylsubstituted by one to five R⁹, dioxo-thietanyl or dioxo-thietanylsubstituted by one to five R⁹, C₁-C₈alkylaminocarbonyl-C₁-C₄ alkylene,C₁-C₈haloalkylaminocarbonyl-C₁-C₄ alkylene, orC₃-C₈cycloalkyl-aminocarbonyl-C₁-C₄ alkylene; for example C₁-C₈alkyl orC₁-C₈alkyl substituted by one to five R⁷, C₃-C₁₀cycloalkyl orC₃-C₁₀cycloalkyl substituted by one to five R⁸, phenyl-C₁-C₄alkylene- orphenyl-C₁-C₄alkylene- wherein the phenyl moiety is substituted by one tofive R⁹, pyridyl-C₁-C₄alkylene- or pyridyl-C₁-C₄alkylene- wherein thepyridyl moiety is substituted by one to four R⁹, oxetanyl or oxetanylsubstituted by one to five R⁹, thietanyl or thietanyl substituted by oneto five R⁹, oxo-thietanyl or oxo-thietanyl substituted by one to fiveR⁹, or dioxo-thietanyl or dioxo-thietanyl substituted by one to five R⁹.

Preferably R² is C₁-C₈alkyl or C₁-C₈alkyl substituted by one to five R⁷,C₃-C₁₀cycloalkyl or C₃-C₁₀cycloalkyl substituted by one or two methylgroups, phenyl-C₁-C₄alkylene- or phenyl-C₁-C₄alkylene- wherein thephenyl moiety is substituted by one to five R⁹, pyridyl-C₁-C₄alkylene-or pyridyl-C₁-C₄alkylene- wherein the pyridyl moiety is substituted byone to four R⁹, imidazolyl-C₁-C₄alkylene or imidazolyl-C₁-C₄alkylenewherein the imidazolyl moiety is substituted by one to five R⁹, oxetanylor oxetanyl substituted by one to five R⁹, thietanyl or thietanylsubstituted by one to five R⁹, oxo-thietanyl or oxo-thietanylsubstituted by one to five R⁹, dioxo-thietanyl or dioxo-thietanylsubstituted by one to five R⁹, for example C₁-C₈alkyl, C₃-C₁₀cycloalkylsubstituted by one or two methyl groups, phenyl-C₁-C₄alkylene- orphenyl-C₁-C₄alkylene- wherein the phenyl moiety is substituted by one tofive R⁹, pyridyl-C₁-C₄alkylene- or pyridyl-C₁-C₄alkylene- wherein thepyridyl moiety is substituted by one to four R⁹, oxetanyl, thietanyl,oxo-thietanyl or dioxo-thietanyl.

Preferably R² is C₃-C₆alkyl or C₃-C₆alkyl substituted by one to five R⁷,C₄-C₈cycloalkyl or C₄-C₈cycloalkyl substituted by one or two methylgroups, phenyl-C₁-C₂alkylene- or phenyl-C₁-C₂alkylene- wherein thephenyl moiety is substituted by one to five R⁹, pyridyl-C₁-C₂alkylene-or pyridyl-C₁-C₂alkylene- wherein the pyridyl moiety is substituted byone to four R⁹, imidazolyl-C₁-C₂alkylene- or imidazolyl-C₁-C₂alkylene-wherein the imidazolyl moiety is substituted by one to five R⁹, oxetanylor oxetanyl substituted by one to five R⁹, thietanyl or thietanylsubstituted by one to five R⁹, oxo-thietanyl or oxo-thietanylsubstituted by one to five R⁹, dioxo-thietanyl or dioxo-thietanylsubstituted by one to five R⁹, more preferably C₃-C₆alkyl or C₃-C₆alkylsubstituted by one to three R⁷, C₄-C₈cycloalkyl, phenyl-methylene- orphenyl-methylene- wherein the phenyl moiety is substituted by one tothree R⁹, imidazolyl-methylene- or imidazolyl-methylene- wherein theimidazolyl moiety is substituted by one to three R⁹, thietanyl ormethylthietanyl, oxo-thietanyl or methyl-oxo-thietanyl, dioxo-thietanylor methyl-dioxo-thietanyl, most preferably butyl, 2,2,2-trifluoroethyl,ethyl, 1-methoxy-prop-2-yl, (1H-benzimidazol-2-yl)-methyl,3,3,3-trifluoropropyl, phenyl-methyl-, (4-methoxy-phenyl)-methyl-,2-methyl-1-methylthio-prop-2-yl, cyclobutyl, bicyclo[2.2.1]heptan-2-yl,thietanyl, methylthietanyl, oxo-thietanyl or dioxo-thietanyl, inparticular thietanyl, oxo-thietanyl or dioxo-thietanyl.

A group of preferred compounds are those wherein R² is C₁-C₆alkyl orC₁-C₆alkyl substituted by one to five R⁷, for example ethyl-, butyl-,but-2-yl-, 3-bromo-propyl-, 2,2,2-trifluoro-ethyl-,3,3,3-trifluoro-propyl-, 2-methyl-1-methylthio-prop-2-yl,2-methoxy-ethyl-, and 1-methoxy-prop-2-yl-, for example ethyl-, butyl-,but-2-yl-, 3-bromo-propyl-, 2,2,2-trifluoro-ethyl-,3,3,3-trifluoro-propyl-, 2-methoxy-ethyl-, and 1-methoxy-prop-2-yl-.

A group of preferred compounds are those wherein R² is C₃-C₈cycloalkylor C₃-C₈cycloalkyl substituted by one to five R⁸, for examplecyclobutyl-, bicyclo[2.2.1]heptan-2-yl and 2-methyl-cyclohex-1-yl-, forexample cyclobutyl- and 2-methyl-cyclohex-1-yl-.

A group of preferred compounds are those wherein R² isaryl-C₁-C₂alkylene- or aryl-C₁-C₂alkylene- wherein the aryl moiety issubstituted by one to five R⁹, for example phenyl-methyl-,1-phenyl-eth-1-yl-, 2-phenyl-eth-1-yl-, (3-chloro-phenyl)-methyl-,(2-fluoro-phenyl)-methyl-, (4-methoxy-phenyl)-methyl-,(2-trifluoromethyl-phenyl)-methyl- and(2-trifluoromethoxy-phenyl)-methyl-.

A group of preferred compounds are those wherein R² isheterocyclyl-C₁-C₂alkylene- or heterocyclyl-C₁-C₂alkylene- wherein theheterocyclyl moiety is substituted by one to five R⁹, for example(pyrid-2-yl)-methyl-, (pyrid-3-yl)-methyl-,(2-chloro-pyrid-5-yl)-methyl-, (1-methyl-1H-imidazol-4-yl)-methyl-,(furan-2-yl)-methyl-, 2-(thiophen-2′-yl)-eth-1-yl-,2-(indol-3′-yl)-eth-1-yl-, (1H-benzimidazol-2-yl)-methyl-,(oxetan-2-yl)-methyl-, (tetrahydro-furan-2-yl)-methyl-,2-([1′,3′]-dioxolan-2′-yl)-eth-1-yl-, 2-(morpholin-4′-yl)-eth-1-yl-,2-(benzo[1′,3′]dioxol-5′-yl)-eth-1-yl-, and(2,3-dihydro-benzo[1,4]dioxin-6-yl)-methyl-, more preferably R² isheteroaryl-C₁-C₂alkylene- or heteroaryl-C₁-C₂alkylene- wherein theheteroaryl moiety is substituted by one to five R⁹.

A group of preferred compounds are those wherein R² is aryl or arylsubstituted by one to five R⁹, for example 2-chloro-phenyl-,3-fluoro-phenyl-, 2-methyl-phenyl-, 2-chloro-6-methyl-phenyl-,2-trifluoromethyl-phenyl-, and 2,4-dimethoxy-phenyl-.

A group of preferred compounds are those wherein R² is heterocyclyl orheterocyclyl substituted by one to five R⁹, for example3-methyl-pyrid-2-yl-, 1,3-dimethyl-1H-pyrazol-5-yl-,4-methyl-thiazol-2-yl-, 5-methyl-thiadiazol-2-yl-, quinolin-2-yl-,quinolin-5-yl-, benzothiazol-6-yl-, 4-methyl-benzothiazol-2-yl-,thietan-3-yl-, 1-oxo-thietan-3-yl-, 1,1-dioxo-thietan-3-yl-, and3-methyl-thietan-3-yl-, more preferably thietan-3-yl-,1-oxo-thietan-3-yl-, 1,1-dioxo-thietan-3-yl- and 3-methyl-thietan-3-yl-.

Preferably R³ is chlorodifluoromethyl or trifluoromethyl, mostpreferably trifluoro-methyl.

Preferably R⁴ is aryl or aryl substituted by one to five R¹⁰, morepreferably aryl substituted by two to three R¹⁰, more preferably phenylsubstituted by two to three R¹⁰, even more preferably3,5-dibromo-phenyl-, 3,5-dichloro-phenyl-, 3,4-dichloro-phenyl-,4-bromo-3,5-dichloro-phenyl or 3,4,5-trichloro-phenyl-, even morepreferably 3,5-dibromo-phenyl-, 3,5-dichloro-phenyl-,3,4-dichloro-phenyl-, or 3,4,5-trichloro-phenyl-, most preferably R⁴ is3,5-dichloro-phenyl.

Preferably each R⁵ is independently hydrogen, halogen, cyano, nitro,C₁-C₈alkyl, C₁-C₈haloalkyl, C₁-C₈alkoxy, or C₁-C₈haloalkoxy, morepreferably hydrogen, bromo, chloro, fluoro, cyano, nitro, methyl, ethyl,trifluoromethyl, methoxy, difluoromethoxy, or trifluoromethoxy, evenmore preferably hydrogen, bromo, chloro, fluoro, nitro, or methyl, morepreferably hydrogen or methyl, most preferably hydrogen.

Preferably each R⁶ is independently hydrogen, methyl or ethyl, morepreferably hydrogen or methyl, most preferably hydrogen.

Preferably each R⁷ is independently halogen, cyano, nitro, hydroxy,C₁-C₈alkoxy, C₁-C₈haloalkoxy, mercapto, C₁-C₈alkylthio-,C₁-C₈haloalkylthio-, more preferably bromo, chloro, fluoro, methyl,methoxy, or methylthio, preferably bromo, chloro, fluoro, methoxy, ormethylthio, most preferably chloro, fluoro, or methoxy.

Preferably each R⁸ is independently chloro, fluoro or methyl, mostpreferably methyl.

Preferably each R⁹ is independently halogen, cyano, nitro, C₁-C₈alkyl,C₁-C₈haloalkyl, C₁-C₈alkoxy, C₁-C₈haloalkoxy, more preferably bromo,chloro, fluoro, cyano, nitro, methyl, ethyl, trifluoromethyl, methoxy,difluoromethoxy, or trifluoromethoxy, preferably bromo, chloro, fluoro,nitro, methoxy or methyl, preferably bromo, chloro, fluoro, nitro, ormethyl, e.g. bromo, chloro, fluoro, methoxy or methyl.

Preferably each R¹⁰ is independently halogen, C₁-C₈alkoxy,C₁-C₈haloalkoxy, C₁-C₈alkylthio-, or C₁-C₈haloalkylthio-, morepreferably bromo, chloro, fluoro, methoxy, or methylthio, mostpreferably bromo or chloro.

Preferably each R¹¹ is independently bromo, chloro, fluoro, cyano,nitro, methyl, ethyl, trifluoromethyl, methoxy, difluoromethoxy, ortrifluoromethoxy, more preferably bromo, chloro, fluoro, nitro, ormethyl, most preferably chloro, fluoro, or methyl.

For example, the present invention provides compounds of formula (I)wherein

A¹, A² and A³ are independently C—R⁵, nitrogen, N—R⁶, oxygen or sulfur,provided that two of A¹, A² or A³ are C—R⁵ or nitrogen and that one ofA¹, A² or A³ is N—R⁶, oxygen or sulfur;

A⁴ and A⁵ are independently C—R⁵ or nitrogen;

G¹ is oxygen or sulfur;

R¹ is hydrogen, C₁-C₈alkyl, C₁-C₈alkylcarbonyl-, orC₁-C₈alkoxycarbonyl-;

R² is C₁-C₈alkyl or C₁-C₈alkyl substituted by one to five R⁷,C₃-C₁₀cycloalkyl or C₃-C₁₀cycloalkyl substituted by one to five R⁸,aryl-C₁-C₄alkylene- or aryl-C₁-C₄alkylene- wherein the aryl moiety issubstituted by one to five R⁹, heterocyclyl-C₁-C₄alkylene- orheterocyclyl-C₁-C₄alkylene- wherein the heterocyclyl moiety issubstituted by one to five R⁹, aryl or aryl substituted by one to fiveR⁹, or heterocyclyl or heterocyclyl substituted by one to five R⁹;

R³ is C₁-C₈haloalkyl;

R⁴ is aryl or aryl substituted by one to five R¹⁰, or heteroaryl orheteroaryl substituted by one to five R¹⁰;

each R⁵ is independently hydrogen, halogen, cyano, nitro, C₁-C₈alkyl,C₁-C₈haloalkyl, C₁-C₈alkoxy, C₁-C₈haloalkoxy, C₁-C₈alkylthio-,C₁-C₈haloalkylthio-, C₁-C₈alkylsulfinyl-, C₁-C₈haloalkylsulfinyl-,C₁-C₈alkylsulfonyl-, or C₁-C₈haloalkylsulfonyl-;

each R⁶ is independently hydrogen or C₁-C₈alkyl;

each R⁷ is independently halogen, cyano, nitro, hydroxy, C₁-C₈alkoxy,C₁-C₈haloalkoxy, mercapto, C₁-C₈alkylthio-, C₁-C₈haloalkylthio-;C₁-C₈alkylsulfinyl-, C₁-C₈haloalkylsulfinyl-, C₁-C₈alkylsulfonyl-, orC₁-C₈haloalkylsulfonyl-;

each R⁸ is independently halogen or C₁-C₈alkyl;

each R⁹ and R¹⁰ is independently halogen, cyano, nitro, C₁-C₈alkyl,C₁-C₈haloalkyl, C₂-C₈alkenyl, C₂-C₈haloalkenyl, C₂-C₈alkynyl,C₂-C₈haloalkynyl, hydroxy, C₁-C₈alkoxy, C₁-C₈haloalkoxy, mercapto,C₁-C₈alkylthio-, C₁-C₈haloalkylthio-, C₁-C₈alkylsulfinyl-,C₁-C₈haloalkylsulfinyl-, C₁-C₈alkylsulfonyl-, C₁-C₈haloalkylsulfonyl-,C₁-C₈alkylcarbonyl-, C₁-C₈alkoxycarbonyl-, aryl or aryl substituted byone to five R¹¹, or heterocyclyl or heterocyclyl substituted by one tofive R¹¹; and

each R¹¹ is independently halogen, cyano, nitro, C₁-C₄alkyl,C₁-C₄haloalkyl, C₁-C₄alkoxy, or C₁-C₄haloalkoxy; or a salt or N-oxidethereof;

provided that -A¹-A²-A³- is not —O—(CR⁵)═N—, —S—(CR⁵)═N—, N═(CR⁵)—O— or—N═(CR⁵)—S— irrespective of the values for A⁴ and A⁵, and

provided that -A¹-A²-A³- is not —(CR⁵)═(CR⁵)—O—, —O—(CR⁵)═(CR⁵)—,—(CR⁵)═(CR⁵)—S—, —S—(CR⁵)═(CR⁵)—, —(CR⁵)═(CR⁵)—(NR⁶)—,—(NR⁶)—(CR⁵)═(CR⁵)—, —(CR⁵)═N—(NR⁶)— and —(NR⁶)—N═(CR⁵)— when A⁴ and A⁵are both C—R⁵.

For example, the present invention provides compounds of formula (I)wherein A¹ and A³ are nitrogen or N—R⁶ and A² is C—R⁵, N—R⁶, nitrogen orsulfur, provided that two of A¹, A² or A³ are C—R⁵ or nitrogen and thatone of A¹, A² or A³ is N—R⁶ or sulfur;

A⁴ and A⁵ are independently C—H or nitrogen;

G¹ is oxygen;

R¹ is hydrogen, methyl, ethyl, methylcarbonyl-, or methoxycarbonyl-;

R² is C₁-C₈alkyl or C₁-C₈alkyl substituted by one to five R⁷,C₃-C₁₀cycloalkyl or C₃-C₁₀cycloalkyl substituted by one to five R⁸,aryl-C₁-C₄alkylene- or aryl-C₁-C₄alkylene- wherein the aryl moiety issubstituted by one to five R⁹, heterocyclyl-C₁-C₄alkylene- orheterocyclyl-C₁-C₄alkylene- wherein the heterocyclyl moiety issubstituted by one to five R⁹, aryl or aryl substituted by one to fiveR⁹, heterocyclyl or heterocyclyl substituted by one to five R⁹,C₁-C₈alkylaminocarbonyl-C₁-C₄ alkylene,C₁-C₈haloalkylaminocarbonyl-C₁-C₄ alkylene, orC₃-C₈cycloalkyl-aminocarbonyl-C₁-C₄ alkylene, wherein each aryl group isa phenyl group and each heterocycle group is selected from pyridyl,pyrazolyl, benzimidazolyl, furanyl, thiazolyl, oxetanyl, thietanyl,oxo-thietanyl and dioxo-thietanyl;

R³ is C₁-C₈haloalkyl;

R⁴ is phenyl substituted by two to three R¹⁰;

R⁵ is independently hydrogen, halogen, cyano, nitro, C₁-C₈alkyl,C₁-C₈haloalkyl, C₁-C₈alkoxy, or C₁-C₈haloalkoxy;

R⁶ is hydrogen or C₁-C₈alkyl;

each R⁷ is independently bromo, chloro, fluoro, methyl, methoxy, ormethylthio;

each R⁸ is independently chloro, fluoro or methyl;

each R⁹ is independently halogen, cyano, nitro, C₁-C₈alkyl,C₁-C₈haloalkyl, C₁-C₈alkoxy or C₁-C₈haloalkoxy;

each R¹⁰ is independently halogen, C₁-C₈alkoxy, C₁-C₈haloalkoxy,C₁-C₈alkylthio-, or C₁-C₈haloalkylthio-.

For example, the present invention provides compounds of formula (I)wherein A¹ and A³ are nitrogen or N—R⁶ and A² is C—R⁵, N—R⁶, nitrogen orsulfur, preferably A² is N—R⁶, nitrogen or sulfur, and provided that twoof A¹, A² or A³ are C—R⁵ or nitrogen and that one of A¹, A² or A³ isN—R⁶ or sulfur;

A⁴ and A⁵ are C—H;

G¹ is oxygen;

R¹ is hydrogen, methyl or ethyl;

R² is C₁-C₈alkyl or C₁-C₈alkyl substituted by one to five R⁷,C₃-C₁₀cycloalkyl or C₃-C₁₀cycloalkyl substituted by one to five R⁸,phenyl-C₁-C₄alkylene- or phenyl-C₁-C₄alkylene- wherein the phenyl moietyis substituted by one to five R⁹, pyridyl-C₁-C₄alkylene- orpyridyl-C₁-C₄alkylene- wherein the pyridyl moiety is substituted by oneto four R⁹, imidazolyl-C₁-C₄alkylene or imidazolyl- C₁-C₄alkylenewherein the imidazolyl moiety is substituted by one to five R⁹, oxetanylor oxetanyl substituted by one to five R⁹, thietanyl or thietanylsubstituted by one to five R⁹, oxo-thietanyl or oxo-thietanylsubstituted by one to five R⁹, dioxo-thietanyl or dioxo-thietanylsubstituted by one to five R⁹, C₁-C₈alkylaminocarbonyl-C₁-C₄ alkylene,C₁-C₈haloalkylaminocarbonyl-C₁-C₄ alkylene, orC₃-C₈cycloalkyl-aminocarbonyl-C₁-C₄ alkylene;

R³ is chlorodifluoromethyl or trifluoromethyl;

R⁴ is 3,5-dibromo-phenyl-, 3,5-dichloro-phenyl-, 3,4-dichloro-phenyl-,4-bromo-3,5-dichloro-phenyl or 3,4,5-trichloro-phenyl-;

R⁵ is independently hydrogen, bromo, chloro, fluoro, cyano, nitro,methyl, ethyl, trifluoromethyl, methoxy, difluoromethoxy, ortrifluoromethoxy;

R⁶ is hydrogen, methyl or ethyl;

each R⁷ is independently bromo, chloro, fluoro, methyl, methoxy, ormethylthio;

each R⁸ is methyl;

each R⁹ is independently bromo, chloro, fluoro, cyano, nitro, methyl,ethyl, trifluoromethyl, methoxy, difluoromethoxy, or trifluoromethoxy.

For example, the present invention provides compounds of formula (I)wherein

-A¹-A²-A³- is selected from ═N—S—N═, —N═C(R⁵)—N(R⁶)—, —N(R⁶)—C(R⁵)═N—,═N—N(R⁶)—N═, —N═N—N(R⁶)— and —N(R⁶)—N═N—, preferably N—S—N═N—N(R⁶)—N═,—N═N—N(R⁶)— and —N(R⁶)—N═N—;

A⁴ and A⁵ are C—H;

G¹ is oxygen;

R¹ is hydrogen;

R² is C₁-C₈alkyl or C₁-C₈alkyl substituted by one to five R⁷,C₃-C₁₀cycloalkyl or C₃-C₁₀cycloalkyl substituted by one or two methylgroups, phenyl-C₁-C₄alkylene- or phenyl-C₁-C₄alkylene- wherein thephenyl moiety is substituted by one to five R⁹, pyridyl-C₁-C₄alkylene-or pyridyl-C₁-C₄alkylene- wherein the pyridyl moiety is substituted byone to four R⁹, imidazolyl-C₁-C₄alkylene or imidazolyl-C₁-C₄alkylenewherein the imidazolyl moiety is substituted by one to five R⁹, oxetanylor oxetanyl substituted by one to five R⁹, thietanyl or thietanylsubstituted by one to five R⁹, oxo-thietanyl or oxo-thietanylsubstituted by one to five R⁹, dioxo-thietanyl or dioxo-thietanylsubstituted by one to five R⁹;

R³ is trifluoromethyl;

R⁴ is 3,5-dichloro-phenyl;

R⁵ is hydrogen or methyl;

R⁶ is hydrogen or methyl;

each R⁷ is independently bromo, chloro, fluoro, methoxy, or methylthio;

each R⁹ is independently bromo, chloro, fluoro, nitro, or methyl.

For example, the present invention provides compounds of formula (I)wherein

-A¹-A²-A³- is selected from ═N—S—N═, —N═C(R⁵)—N(R⁶)—, ═N—N(R⁶)—N═, and—N═N—N(R⁶)—, preferably ═N—S—N═, ═N—N(R⁶)—N═, and —N═N—N(R⁶)—;

A⁴ and A⁵ are C—H;

G¹ is oxygen;

R¹ is hydrogen;

R² is C₃-C₆alkyl or C₃-C₆alkyl substituted by one to five R⁷,C₄-C₈cycloalkyl or C₄-C₈cycloalkyl substituted by one or two methylgroups, phenyl-C₁-C₂alkylene- or phenyl-C₁-C₂alkylene- wherein thephenyl moiety is substituted by one to five R⁹, pyridyl-C₁-C₂alkylene-or pyridyl-C₁-C₂alkylene- wherein the pyridyl moiety is substituted byone to four R⁹, imidazolyl-C₁-C₂alkylene- or imidazolyl-C₁-C₂alkylene-wherein the imidazolyl moiety is substituted by one to five R⁹, oxetanylor oxetanyl substituted by one to five R⁹, thietanyl or thietanylsubstituted by one to five R⁹, oxo-thietanyl or oxo-thietanylsubstituted by one to five R⁹, dioxo-thietanyl or dioxo-thietanylsubstituted by one to five R⁹;

R³ is trifluoromethyl;

R⁴ is 3,5-dichloro-phenyl;

R⁵ is hydrogen or methyl;

R⁶ is hydrogen or methyl;

each R⁷ is independently bromo, chloro, fluoro, methoxy, or methylthio;

each R⁹ is independently bromo, chloro, fluoro, methoxy or methyl.

For example, the present invention provides compounds of formula (I)wherein

-A¹-A²-A³- is ═N—S—N═;

A⁴ and A⁵ are CH;

G¹ is oxygen;

R¹ is hydrogen;

R² is C₃-C₆alkyl or C₃-C₆alkyl substituted by one to three R⁷,C₄-C₈cycloalkyl, phenyl-methylene- or phenyl-methylene- wherein thephenyl moiety is substituted by one to three R⁹, imidazolyl-methylene-or imidazolyl-methylene- wherein the imidazolyl moiety is substituted byone to three R⁹, thietanyl or methylthietanyl, oxo-thietanyl ormethyl-oxo-thietanyl, dioxo-thietanyl or methyl-dioxo-thietanyl;

R³ is trifluoromethyl;

R⁴ is 3,5-dichloro-phenyl;

R⁶ is hydrogen or methyl;

each R⁷ is independently bromo, chloro, fluoro, methoxy, or methylthio;

each R⁹ is independently bromo, chloro, fluoro, methoxy or methyl.

A preferred embodiment are compounds of formula (IA) wherein A¹ is N, A²is S and A³ is N, A⁴ is C—H, A⁵ is C—H, and G¹, R¹, R², R³, R⁴, R⁶, R⁷,R⁸, and R⁹ are as defined for a compound of formula (I); or a salt orN-oxide thereof.

A preferred embodiment are compounds of formula (IB) wherein A¹ is N, A²is C—H and A³ is N—H, A⁴ is C—H, A⁵ is C—H, and G¹, R¹, R², R³, R⁴, R⁶,R⁷, R⁸, and R⁹ are as defined for a compound of formula (I); or a saltor N-oxide thereof.

A preferred embodiment are compounds of formula (IC) wherein A¹ is N, A²is C—H and A³ is N-Me, A⁴ is C—H, A⁵ is C—H, and G¹, R¹, R², R³, R⁴, R⁶,R⁷, R⁸, and R⁹ are as defined for a compound of formula (I); or a saltor N-oxide thereof.

A preferred embodiment are compounds of formula (ID) wherein A¹ is N, A²is N and A³ is N—H, A⁴ is C—H, A⁵ is C—H, and G¹, R¹, R², R³, R⁴, R⁶,R⁷, R⁸, and R⁹ are as defined for a compound of formula (I); or a saltor N-oxide thereof.

A preferred embodiment are compounds of formula (IE) wherein A¹ is N, A²is N and A³ is N-Me, A⁴ is C—H, A⁵ is C—H, and G¹, R¹, R², R³, R⁴, R⁶,R⁷, R⁸, and R⁹ are as defined for a compound of formula (I); or a saltor N-oxide thereof.

Certain intermediates are novel and as such form a further aspect of theinvention. One group of novel intermediates are compounds of formula(II)

wherein A¹, A², A³, A⁴, A⁵, G¹, R³ and R⁴ are as defined for a compoundof formula (I), and R is hydroxy, C₁-C₆alkoxy or halogen, such as bromo,chloro or fluoro; or a salt or N-oxide thereof. The preferences for A¹,A², A³, A⁴, A⁵, G¹, R³ and R⁴ are the same as the preferences set outfor the corresponding substituents of a compound of formula (I).Preferably R is hydroxy, C₁-C₆alkoxy or chloro.

A further group of novel intermediates are compounds of formula (IV)

wherein A¹, A², A³, A⁴, A⁵, R³ and R⁴ are as defined for a compound offormula (I), and X^(B) is halogen, such as bromo, chloro or fluoro; or asalt or N-oxide thereof. The preferences for A¹, A², A³, A⁴, A⁵, R³ andR⁴ are the same as the preferences set out for the correspondingsubstituents of a compound of formula (I). Preferably X^(B) is bromo.

A further group of novel intermediates are compounds of formula (XI)

wherein A¹, A², A³, A⁴, A⁵, G¹, R¹ and R² are as defined for a compoundof formula (I); or a salt or N-oxide thereof. The preferences for A¹,A², A³, A⁴, A⁵, G¹, R¹ and R² are the same as the preferences set outfor the corresponding substituents of a compound of formula (I).

A further group of novel intermediates are compounds of formula (XII)

wherein A¹, A², A³, A⁴, A⁵, G¹, R¹ and R² are as defined for a compoundof formula (I); or a salt or N-oxide thereof. The preferences for A¹,A², A³, A⁴, A⁵, G¹, R¹ and R² are the same as the preferences set outfor the corresponding substituents of a compound of formula (I).

A further group of novel intermediates are compounds of formula (XIV)

wherein A¹, A², A³, A⁴, A⁵, G¹, R¹ and R² are as defined for a compoundof formula (I); or a salt or N-oxide thereof. The preferences for A¹,A², A³, A⁴, A⁵, G¹, R¹ and R² are the same as the preferences set outfor the corresponding substituents of a compound of formula (I).

A further group of novel intermediates are compounds of formula (XV)

wherein A¹, A², A³, A⁴, A⁵, G¹, R¹ and R² are as defined for a compoundof formula (I); or a salt or N-oxide thereof. The preferences for A¹,A², A³, A⁴, A⁵, G¹, R¹ and R² are the same as the preferences set outfor the corresponding substituents of a compound of formula (I).

A further group of novel intermediates are compounds of formula (XVIII)

wherein A¹, A², A³, A⁴, A⁵, G¹, R¹ and R² are as defined for a compoundof formula (I); or a salt or N-oxide thereof. The preferences for A¹,A², A³, A⁴, A⁵, G¹, R¹ and R² are the same as the preferences set outfor the corresponding substituents of a compound of formula (I).

A further group of novel intermediates are compounds of formula (XIX)

wherein A¹, A², A³, A⁴, A⁵, G¹, R¹, R², R³ and R⁴ are as defined for acompound of formula (I); or a salt or N-oxide thereof. The preferencesfor A¹, A², A³, A⁴, A⁵, G¹, R¹, R², R³ and R⁴ are the same as thepreferences set out for the corresponding substituents of a compound offormula (I).

A further group of novel intermediates are compounds of formula (XX)

wherein A¹, A², A³, A⁴, A⁵, G¹, R¹, R², R³ and R⁴ are as defined for acompound of formula (I); or a salt or N-oxide thereof. The preferencesfor A¹, A², A³, A⁴, A⁵, G¹, R¹, R², R³ and R⁴ are the same as thepreferences set out for the corresponding substituents of a compound offormula (I).

A further group of novel intermediates are compounds of formula (XXII)

wherein A¹, A², A³, A⁴, A⁵, G¹, R¹ and R² are as defined for a compoundof formula (I); or a salt or N-oxide thereof. The preferences for A¹,A², A³, A⁴, A⁵, G¹, R¹ and R² are the same as the preferences set outfor the corresponding substituents of a compound of formula (I).

A further group of novel intermediates are compounds of formula (XXIII)

wherein A¹, A², A³, A⁴, A⁵, G¹, R¹ and R² are as defined for a compoundof formula (I), and Hal is a halogen, such as such as bromo or chloro;or a salt or N-oxide thereof. The preferences for A¹, A², A³, A⁴, A⁵,G¹, R¹ and R² are the same as the preferences set out for thecorresponding substituents of a compound of formula (I).

A further group of novel intermediates are compounds of formula (XXIV)

wherein A¹, A², A³, A⁴, A⁵, G¹, R¹, R², R³ and R⁴ are as defined for acompound of formula (I); or a salt or N-oxide thereof. The preferencesfor A¹, A², A³, A⁴, A⁵, G¹, R¹, R², R³ and R⁴ are the same as thepreferences set out for the corresponding substituents of a compound offormula (I).

In a further aspect, the present invention provides a compound offormula (A)

wherein

A¹, A² and A³ are independently C—R⁵, nitrogen, N—R⁶, oxygen or sulfur,provided that two of A¹, A² or A³ are C—R⁵ or nitrogen and that one ofA¹, A² or A³ is N—R⁶, oxygen or sulfur;

A⁴ and A⁵ are independently C—R⁵ or nitrogen;

G¹ is oxygen or sulfur;

R¹ is hydrogen, C₁-C₈alkyl, C₁-C₈alkylcarbonyl-, orC₁-C₈alkoxycarbonyl-;

R² is cyclobutyl or cyclobutyl substituted by one to five R⁸, oxetanylor oxetanyl substituted by one to five R⁹, thietanyl or thietanylsubstituted by one to five R⁹, oxo-thietanyl or oxo-thietanylsubstituted by one to five R⁹, or dioxo-thietanyl or dioxo-thietanylsubstituted by one to five R⁹;

R³ is C₁-C₈haloalkyl;

R⁴ is aryl or aryl substituted by one to five R¹⁰, or heteroaryl orheteroaryl substituted by one to five R¹⁰;

each R⁵ is independently hydrogen, halogen, cyano, nitro, C₁-C₈alkyl,C₁-C₈haloalkyl, C₁-C₈alkoxy, C₁-C₈haloalkoxy, C₁-C₈alkylthio-,C₁-C₈haloalkylthio-, C₁-C₈alkylsulfinyl-, C₁-C₈haloalkylsulfinyl-,C₁-C₈alkylsulfonyl-, or C₁-C₈haloalkylsulfonyl-;

each R⁶ is independently hydrogen or C₁-C₈alkyl;

each R⁸ is independently halogen or C₁-C₈alkyl;

each R⁹ and R¹⁰ is independently halogen, cyano, nitro, C₁-C₈alkyl,C₁-C₈haloalkyl, C₂-C₈alkenyl, C₂-C₈haloalkenyl, C₂-C₈alkynyl,C₂-C₈haloalkynyl, hydroxy, C₁-C₈alkoxy, C₁-C₈haloalkoxy, mercapto,C₁-C₈alkylthio-, C₁-C₈haloalkylthio-, C₁-C₈alkylsulfinyl-,C₁-C₈haloalkylsulfinyl-, C₁-C₈alkylsulfonyl-, C₁-C₈haloalkylsulfonyl-,C₁-C₈alkylcarbonyl-, C₁-C₈alkoxycarbonyl-, aryl or aryl substituted byone to five R¹¹, or heterocyclyl or heterocyclyl substituted by one tofive R¹¹; and

each R¹¹ is independently halogen, cyano, nitro, C₁-C₄alkyl,C₁-C₄haloalkyl, C₁-C₄alkoxy, or C₁-C₄haloalkoxy; or a salt or N-oxidethereof;

Preferably A¹ is nitrogen, C—R⁵ or N—R⁶, most preferably nitrogen orN—CH₃.

Preferably A² is C—R⁵, nitrogen or sulfur.

Preferably A³ is nitrogen C—R⁵ or N—R⁶, most preferably nitrogen orN—CH₃.

Preferably -A¹-A²-A³- is selected from ═N—S—N═, —S—N═N—, —N═N—S—,═N—N(R⁶)—N═, —N═N—N(R⁶)—, —N(R⁶)—N═N—, —C(R⁵)═N—N(R⁶)—, —N(R⁶)—N═C(R⁵)—,—N═C(R⁵)—N(R⁶)—, —N(R⁶)—C(R⁵)═N—, —N═C(R⁵)—O—, —O—C(R⁵)═N—, ═N—O—C(R⁵)═and ═C(R⁵)—O—N═, more preferably -A¹-A²-A³- is selected from ═N—S—N═,—S—N═N—, —N═N—S—, ═N—N(R⁶)—N═, —N═N—N(R⁶)—, —N(R⁶)—N═N—,—C(R⁵)═N—N(R⁶)—, —N(R⁶)—N═C(R⁵)—, —N═C(R⁵)—N(R⁶)—, —N(R⁶)—C(R⁵)═N—,—N═C(R⁵)—O— and —O—C(R⁵)═N—, more preferably ═N—S—N═, —N═C(R⁵)—N(R⁶)—,—N═N—N(R⁶)—, ═N—N(R⁶)—N═, —C(R⁵)═N—N(R⁶)— and —N═C(R⁵)—O—, morepreferably ═N—S—N═, —N═C(R⁵)—N(R⁶)—, —N═N—N(R⁶)—, ═N—N(R⁶)—N═ and—C(R⁵)═N—N(R⁶)—, more preferably ═N—S—N═, —N═N—N(R⁶)— and ═N—N(R⁶)—N═,most preferably ═N—S—N═.

R² is preferably cyclobutyl or cyclobutyl substituted by one to five R⁸,thietanyl or thietanyl substituted by one to five R⁹, oxo-thietanyl oroxo-thietanyl substituted by one to five R⁹, or dioxo-thietanyl ordioxo-thietanyl substituted by one to five R⁹, more preferably thietanylor methylthietanyl, oxo-thietanyl or methyl-oxothietanyl,dioxo-thietanyl or methyl-dioxo-thietanyl, more preferably thietanyl,oxo-thietanyl or dioxo-thietanyl.

The preferred definitions for A⁴, A⁵, G¹, R¹, R³, R⁴, R⁵, R⁶, R⁸, R⁹,R¹⁰ and R¹¹ are as described for compounds of formula (A).

For example, the present invention provides compounds of formula (A)wherein

-A¹-A²-A³- is selected from ═N—S—N═, —S—N═N—, —N═N—S—, ═N—N(R⁶)—N═,—N═N—N(R⁶)—, —N(R⁶)—N═N—, —C(R⁵)═N—N(R⁶)—, —N(R⁶)—N═C(R⁵)—,—N═C(R⁵)—N(R⁶)—, —N(R⁶)—C(R⁵)═N—, —N═C(R⁵)—O— and —O—C(R⁵)═N—;

A⁴ and A⁵ are independently C—H or nitrogen;

G¹ is oxygen;

R¹ is hydrogen, methyl, ethyl, methylcarbonyl-, or methoxycarbonyl-;

R² is cyclobutyl or cyclobutyl substituted by one to five R⁸, oxetanylor oxetanyl substituted by one to five R⁹, thietanyl or thietanylsubstituted by one to five R⁹, oxo-thietanyl or oxo-thietanylsubstituted by one to five R⁹, or dioxo-thietanyl or dioxo-thietanylsubstituted by one to five R⁹;

R³ is C₁-C₈haloalkyl;

R⁴ is phenyl substituted by two to three R¹⁰;

R⁵ is hydrogen, bromo, chloro, fluoro, cyano, nitro, methyl, ethyl,trifluoromethyl, methoxy, difluoromethoxy, or trifluoromethoxy;

R⁶ is hydrogen or C₁-C₈alkyl;

each R⁸ is independently chloro, fluoro or methyl;

each R⁹ is independently halogen, cyano, nitro, C₁-C₈alkyl,C₁-C₈haloalkyl, C₁-C₈alkoxy, C₁-C₈haloalkoxy;

each R¹⁰ is independently halogen, C₁-C₈alkoxy, C₁-C₈haloalkoxy,C₁-C₈alkylthio-, or C₁-C₈haloalkylthio-.

For example, the present invention provides compounds of formula (A)wherein

-A¹-A²-A³- is selected from ═N—S—N═, —N═C(R⁵)—N(R⁶)—, —N═N—N(R⁶)—,═N—N(R⁶)—N═, —C(R⁵)═N—N(R⁶)— and —N═C(R⁵)—O—;

A⁴ and A⁵ are C—H;

G¹ is oxygen;

R¹ is hydrogen, methyl or ethyl;

R² is cyclobutyl or cyclobutyl substituted by one to five R⁸, oxetanylor oxetanyl substituted by one to five R⁹, thietanyl or thietanylsubstituted by one to five R⁹, oxo-thietanyl or oxo-thietanylsubstituted by one to five R⁹, or dioxo-thietanyl or dioxo-thietanylsubstituted by one to five R⁹;

R³ is chlorodifluoromethyl or trifluoromethyl;

R⁴ is 3,5-dibromo-phenyl-, 3,5-dichloro-phenyl-, 3,4-dichloro-phenyl- or3,4,5-trichloro-phenyl-, most preferably R⁴ is 3,5-dichloro-phenyl;

R⁵ is hydrogen, bromo, chloro, fluoro, nitro, or methyl

R⁶ is hydrogen, methyl or ethyl;

each R⁸ is methyl;

each R⁹ is independently bromo, chloro, fluoro, cyano, nitro, methyl,ethyl, trifluoromethyl, methoxy, difluoromethoxy, or trifluoromethoxy.

For example, the present invention provides compounds of formula (A)wherein

-A¹-A²-A³- is selected from ═N—S—N═, —N═C(R⁵)—N(R⁶)—, —N═N—N(R⁶)—,═N—N(R⁶)—N═ and —C(R⁵)═N—N(R⁶)—;

A⁴ and A⁵ are C—H;

G¹ is oxygen;

R¹ is hydrogen;

R² is cyclobutyl, thietanyl or methylthietanyl, oxo-thietanyl ormethyl-oxo-thietanyl, or dioxo-thietanyl or methyl-dioxo-thietanyl;

R³ is trifluoromethyl;

R⁴ is 3,5-dichloro-phenyl;

R⁵ is hydrogen or methyl;

R⁶ is hydrogen or methyl.

Any reference herein to uses and/or compositions of compounds of formula(I) also applies equally to compounds of formula (A).

The compounds in Tables 1 to 5 below illustrate the compounds of theinvention.

TABLE 1 Table 1 provides 51 compounds of formula (Ia) wherein G¹ isoxygen, R³ is trifluoromethyl, R⁴ is 3,5-dichloro-phenyl-, and R¹ and R²have the values listed in the table below. (Ia)

Compound numbers R¹ R² 1.01 H ethyl- 1.02 H butyl- 1.03 H but-2-yl- 1.04H 3-bromo-propyl- 1.05 H 2,2,2-trifluoro-ethyl- 1.06 H3,3,3-trifluoro-propyl- 1.07 H 2-methoxy-ethyl- 1.08 H1-methoxy-prop-2-yl- 1.09 H cyclobutyl- 1.10 H 2-methyl-cyclohex-1-yl-1.11 H phenyl-methyl- 1.12 H 1-phenyl-eth-1-yl- 1.13 H2-phenyl-eth-1-yl- 1.14 H (3-chloro-phenyl)-methyl- 1.15 H(2-fluoro-phenyl)-methyl- 1.16 H (4-methoxy-phenyl)-methyl- 1.17 H(2-trifluoromethyl-phenyl)-methyl- 1.18 H(2-trifluoromethoxy-phenyl)-methyl- 1.19 H (pyrid-2-yl)-methyl- 1.20 H(pyrid-3-yl)-methyl- 1.21 H (2-chloro-pyrid-5-yl)-methyl- 1.22 H(1-methyl-1H-imidazol-4-yl)-methyl- 1.23 H (furan-2-yl)-methyl- 1.24 H2-(thiophen-2′-yl)-eth-1-yl- 1.25 H 2-(indol-3′-yl)-eth-1-yl- 1.26 H(1H-benzimidazol-2-yl)-methyl- 1.27 H (oxetan-2-yl)-methyl- 1.28 H(tetrahydrofuran-2-yl)-methyl- 1.29 H2-([1′,3′]dioxolan-2′-yl)-eth-1-yl- 1.30 H 2-(morpholin-4′-yl)-eth-1-yl-1.31 H 2-(benzo[1′,3′]dioxol-5′-yl)-eth-1-yl- 1.32 H(2,3-dihydro-benzo[1,4]dioxin-6-yl)-methyl- 1.33 H 2-chloro-phenyl- 1.34H 3-fluoro-phenyl- 1.35 H 2-methyl-phenyl- 1.36 H2-chloro-6-methyl-phenyl- 1.37 H 2-trifluoromethyl-phenyl- 1.38 H2,4-dimethoxy-phenyl- 1.39 H 3-methyl-pyrid-2-yl- 1.40 H1,3-dimethyl-1H-pyrazol-5-yl- 1.41 H 4-methyl-thiazol-2-yl- 1.42 H5-methyl-thiadiazol-2-yl- 1.43 H quinolin-2-yl- 1.44 H quinolin-5-yl-1.45 H benzothiazol-6-yl- 1.46 H 4-methyl-benzothiazol-2-yl- 1.47 Hthietan-3-yl- 1.48 H 1-oxo-thietan-3-yl- 1.49 H 1,1-dioxo-thietan-3-yl-1.50 H 3-methyl-thietan-3-yl- 1.51 HN-(2,2,2-Trifluoro-ethyl)-acetamide-2-yl

TABLE 2 Table 2 provides 51 compounds of formula (Ib) wherein G¹ isoxygen, R³ is trifluoromethyl, R⁴ is 3,5-dichloro-phenyl-, and R¹ and R²have the values listed in Table 1 above. (Ib)

TABLE 3 Table 3 provides 51 compounds of formula (Ic) wherein G¹ isoxygen, R³ is trifluoromethyl, R⁴ is 3,5-dichloro-phenyl-, and R¹ and R²have the values listed in Table 1 above. (Ic)

TABLE 4 Table 4 provides 51 compounds of formula (Id) wherein G¹ isoxygen, R³ is trifluoromethyl, R⁴ is 3,5-dichloro-phenyl-, and R¹ and R²have the values listed in Table 1 above. (Id)

TABLE 5 Table 5 provides 51 compounds of formula (Ie) wherein G¹ isoxygen, R³ is trifluoromethyl, R⁴ is 3,5-dichloro-phenyl-, and R¹ and R²have the values listed in Table 1 above. (Ie)

TABLE 6 Table 6 provides 51 compounds of formula (If) wherein G¹ isoxygen, R³ is trifluoromethyl, R⁴ is 3,5-dichloro-phenyl-, and R¹ and R²have the values listed in Table 1 above. (If)

TABLE 7 Table 7 provides 5 compounds of formula (Ig) wherein G¹ isoxygen, R³ is trifluoromethyl, R⁴ is 3,5-dichloro-phenyl-, and R¹ and R²have the values listed below. (Ig)

Compound numbers R¹ R² 7.01 H cyclobutyl- 7.02 H thietan-3-yl- 7.03 H1-oxo-thietan-3-yl- 7.04 H 1,1-dioxo-thietan-3-yl- 7.05 H3-methyl-thietan-3-yl-

TABLE 8 Table 7 provides 5 compounds of formula (Ih) wherein G¹ isoxygen, R³ is trifluoromethyl, R⁴ is 3,5-dichloro-phenyl-, and R¹ and R²have the values listed in Table 7 above. Ih

The compounds of the invention may be made by a variety of methods asshown in Schemes 1 to 8.

1) Compounds of formula (I) wherein G¹ is oxygen, can be prepared byreacting a compound of formula (II) wherein G¹ is oxygen and R is OH,C₁-C₆alkoxy or Cl, F or Br, with an amine of formula (III) as shown inScheme 1. When R is OH such reactions are usually carried out in thepresence of a coupling reagent, such as N,N′-dicyclohexylcarbo-diimide(“DCC”), 1-ethyl-3-(3-dimethylamino-propyl)carbodiimide hydrochloride(“EDC”) or bis(2-oxo-3-oxazolidinyl)phosphonic chloride (“BOP-Cl”), inthe presence of a base, and optionally in the presence of a nucleophiliccatalyst, such as hydroxybenzotriazole (“HOBT”). When R is Cl, suchreactions are usually carried out in the presence of a base, andoptionally in the presence of a nucleophilic catalyst. Alternatively, itis possible to conduct the reaction in a biphasic system comprising anorganic solvent, preferably ethyl acetate, and an aqueous solvent,preferably a solution of sodium hydrogen carbonate. When R isC₁-C₆alkoxy it is sometimes possible to convert the ester directly tothe amide by heating the ester and amine together in a thermal process.Suitable bases include pyridine, triethylamine,4-(dimethylamino)-pyridine (“DMAP”) or diisopropylethylamine (Hunig'sbase). Preferred solvents are N,N-dimethylacetamide, tetrahydrofuran,dioxane, 1,2-dimethoxyethane, ethyl acetate and toluene. The reaction iscarried out at a temperature of from 0° C. to 100° C., preferably from15° C. to 30° C., in particular at ambient temperature. Amines offormula (III) are either commercially available or known in theliterature, or can be prepared using methods known to a person skilledin the art.

2) Acid halides of formula (II), wherein G¹ is oxygen and R is Cl, F orBr, may be made from carboxylic acids of formula (II), wherein G¹ isoxygen and R is OH, under standard conditions, such as treatment withthionyl chloride or oxalyl chloride. A preferred solvent isdichloromethane. The reaction is carried out at a temperature of from 0°C. to 100° C., preferably from 15° C. to 30° C., in particular atambient temperature.

3) Carboxylic acids of formula (II), wherein G¹ is oxygen and R is OH,may be formed from esters of formula (II), wherein G¹ is oxygen and R isC₁-C₆alkoxy. It is known to a person skilled in the art that there aremany methods for the hydrolysis of such esters depending on the natureof the alkoxy group. One widely used method to achieve such atransformation is the treatment of the ester with an alkali hydroxide,such as lithium hydroxide, sodium hydroxide or potassium hydroxide, in asolvent, such as ethanol or tetrahydrofuran, in the presence of water.Another is the treatment of the ester with an acid, such astrifluoroacetic acid, in a solvent, such as dichloromethane, followed byaddition of water. The reaction is carried out at a temperature of from0° C. to 150° C., preferably from 15° C. to 100° C., in particular at50° C.

4) Compounds of formula (II) wherein G¹ is oxygen and R is C₁-C₆alkoxy,can be prepared by reacting a compound of formula (IV) wherein X^(B) isa leaving group, for example a halogen, such as bromo, with carbonmonoxide and an alcohol of formula R—OH, such as ethanol, in thepresence of a catalyst, such asbis(triphenylphosphine)palladium(II)dichloride, and in the presence of abase, such as pyridine, triethylamine, 4-(dimethylamino)-pyridine(“DMAP”) or diisopropylethylamine (Hunig's base). The reaction iscarried out at a temperature of from 50° C. to 200° C., preferably from100° C. to 150° C., in particular at 115° C. The reaction is carried outat a pressure of from 50 to 200 bar, preferably from 100 to 150 bar, inparticular at 120 bar.

5) Alternatively, compounds of formula (I) wherein G¹ is oxygen, can beprepared by reacting a compound of formula (IV) wherein X^(B) is aleaving group, for example a halogen, such as bromo, with carbonmonoxide and an amine of formula (III), in the presence of a catalyst,such as palladium(II) acetate orbis(triphenylphosphine)palladium(II)dichloride, in the presence of abase, such as sodium carbonate, pyridine, triethylamine,4-(dimethyl-amino)-pyridine (“DMAP”) or diisopropylethylamine (Hunig'sbase), optionally in the presence of a ligand, such astriphenylphosphine, in a solvent, such as water, N,N-dimethylformamideor tetrahydrofuran. The reaction is carried out at a temperature of from50° C. to 200° C., preferably from 100° C. to 150° C. The reaction iscarried out at a pressure of from 50 to 200 bar, preferably from 100 to150 bar.

6) Compounds of formula (IV) wherein X^(B) is a leaving group, forexample a halogen, such as bromo, can be made by reaction of an oxime offormula (V) wherein X^(B) is a leaving group, for example a halogen,such as bromo, and a vinyl compound of formula (VI) in a two stepreaction. In the first step, the oxime of formula (V) is reacted with ahalogenating agent, for example a succinimide, such asN-chlorosuccinimide (“NCS”), in the presence of a suitable solvent, forexample a polar solvent, such as N,N-dimethylformamide. The first stepis carried out at a temperature of from 0° C. to 100° C., preferablyfrom 15° C. to 30° C., in particular at ambient temperature.

In the second step, the chloro hydroxy imine intermediate of formula(V′) is reacted with the vinyl compound of formula (VI) in the presenceof a base, for example an organic base, such as triethylamine, or aninorganic base, such as sodium hydrogen carbonate, in the presence of asuitable solvent, for example a polar solvent, such asN,N-dimethylformamide or isopropanol. It is possible to conduct thesetwo steps separately and optionally to isolate the chloro hydroxy imineintermediate or more conveniently to conduct these two stepssuccessively in one reaction vessel without isolation of theintermediate. The second step is carried out at a temperature of from 0°C. to 100° C., preferably from 15° C. to 30° C., in particular atambient temperature. Vinyl compounds of formula (VI) are commerciallyavailable or can be made by methods known to a person skilled in theart.

7) Compounds of formula (V) wherein X^(B) is a leaving group, forexample a halogen, such as bromo, can be made by reaction of an aldehydeof formula (VII) wherein X^(B) is a leaving group, for example ahalogen, such as bromo, with a hydroxylamine, such as hydroxylaminehydrochloride. Such reactions are carried out optionally in the presenceof a base, for example an organic base, such as triethylamine or sodiumacetate, or an inorganic base, such as sodium hydrogen carbonate,optionally in the presence of a solvent, such as methanol, ethanol orwater, or a mixture thereof. The reaction is carried out at atemperature of from 0° C. to 100° C., preferably from 15° C. to 30° C.,in particular at ambient temperature. Aldehydes of formula (VII) arecommercially available or can be made by methods known to a personskilled in the art.

8) Compounds of formula (I), wherein G¹ is sulfur, may be made bytreatment of a compound of formula (II), wherein G¹ is oxygen and R isOH, C₁-C₆alkoxy or Cl, F or Br, with a thio-transfer reagent, such asLawesson's reagent or phosphorus pentasulfide, prior to elaborating tocompounds of formula (I), as described under 1).

9) Compounds of formula (I) with a sulfoxide group or a sulfone groupcan be made from a compound of formula (I) with a sulfide group (orsulfoxide group) in the corresponding position, by treatment with anoxidising reagent, such as potassium permanganate, 3-chloroperoxybenzoicacid (“MCPBA”), sodium periodate (optionally in the presence ofruthenium(II) oxide), hydrogen peroxide, oxone and sodium hypochlorite.One equivalent of oxidising reagent is required to convert a sulfide toa sulfoxide, or a sulfoxide to a sulfone. Two equivalents of oxidisingreagent are required to convert a sulfide to a sulfone. Preferredsolvents are tetrahydrofuran, dioxane, 1,2-dimethoxyethane, ethylacetate, toluene, dichloromethane and water, or mixtures thereof. Thereaction is optionally carried out in the presence of a base, forexample a carbonate, such as sodium hydrogen carbonate. The reaction iscarried out at a temperature of from 0° C. to 100° C., preferably from15° C. to 30° C., in particular at ambient temperature.

10) Alternatively, compounds of formula (II) wherein G¹ is oxygen and Ris C₁-C₆alkoxy, such as methoxy or tert-butoxy, can be prepared byreaction of an oxime of formula (VIII) wherein G¹ is oxygen and R isC₁-C₆alkoxy, such as methoxy or tert-butoxy, with a halogenating agentfollowed by a vinyl compound of formula (VI) and base as shown in Scheme2 in a two step reaction as described under 6). The intermediate offormula (VIII′), wherein G¹ is oxygen and R is C₁-C₆alkoxy, such asmethoxy or tert-butoxy, can optionally be isolated.

11) Compounds of formula (VIII) wherein G¹ is oxygen and R isC₁-C₆alkoxy, such as methoxy or tert-butoxy, can be made by reaction ofan aldehyde of formula (IX) wherein G¹ is oxygen and R is C₁-C₆alkoxy,for example methoxy or tert-butoxy, with a hydroxylamine as describedunder 7).

12) Compounds of formula (IX) wherein G¹ is oxygen and R is C₁-C₆alkoxy,such as methoxy or tert-butoxy, can be prepared by reaction of acompound of formula (X) wherein G¹ is oxygen, R is C₁-C₆alkoxy, forexample methoxy or tert-butoxy, and X^(B) is a leaving group, forexample a halogen, such as bromo, with a formylating agent, such asN,N-dimethylformamide. Such reactions are carried out in the presence ofa base, for example a lithium base, such as butyl lithium, in thepresence of a suitable solvent, for example a polar solvent, such astetrahydrofuran or excess N,N-dimethylformamide. Compounds of formula(X) wherein G¹ is oxygen and R is C₁-C₆alkoxy, such as methoxy ortert-butoxy, are commercially available or can be made by methods knownto a person skilled in the art.

13) Alternatively, compounds of formula (I) wherein G¹ is oxygen, can beprepared by reaction of an oxime of formula (XI) wherein G¹ is oxygen,with a halogenating agent followed by a vinyl compound of formula (VI)and base as shown in Scheme 3 in a two step reaction as described under6). The intermediate of formula (XI′) wherein G¹ is oxygen, canoptionally be isolated.

14) Compounds of formula (XI) wherein G¹ is oxygen, can be made byreaction of an aldehyde of formula (XII) wherein G¹ is oxygen, with ahydroxylamine as described under 7).

15) Compounds of formula (XII) wherein G¹ is oxygen, can be prepared byreaction of a compound of formula (XIII) wherein G¹ is oxygen and X^(B)is a leaving group, for example a halogen, such as bromo, with aformylating agent and a base as described under 12).

16) Compounds of formula (XIII) wherein G¹ is oxygen and X^(B) is aleaving group, for example a halogen, such as bromo, can be prepared byreacting an acid derivative of formula (X) wherein G¹ is oxygen and R isOH, C₁-C₆alkoxy or Cl, F or Br, and X^(B) is a leaving group, forexample a halogen, such as bromo, with an amine of formula (III) asdescribed under 1).

17) Alternatively, compounds of formula (I) wherein G¹ is oxygen, can bemade by reaction of an N-hydroxy-amidine of formula (XIV) wherein G¹ isoxygen, and a vinyl compound of formula (VI) in a two step reaction asshown in Scheme 4. In the first step, the N-hydroxy-amidine of formula(XIV), wherein G¹ is oxygen, is reacted with a nitrosylating agent, suchas sodium nitrite, in the presence of an acid, such as aqueoushydrochloric acid. The first step is carried out at a temperature offrom −20° C. to +30° C., preferably from −5° C. to +10° C.

In the second step, the chloro hydroxy imine intermediate of formula(XI′) wherein G¹ is oxygen, is reacted with the vinyl compound offormula (VI) in the presence of a base, for example an organic base,such as triethylamine, or an inorganic base, such as sodium hydrogencarbonate, in the presence of a suitable solvent, for example a polarsolvent, such as N,N-dimethylformamide or isopropanol. It is possible toconduct these two steps separately and optionally to isolate the chlorohydroxy imine intermediate or more conveniently to conduct these twosteps successively in one reaction vessel without isolation of theintermediate. The second step is carried out at a temperature of from 0°C. to 100° C., preferably from 15° C. to 30° C., in particular atambient temperature.

18) Compounds of formula (XIV) wherein G¹ is oxygen, can be made byreaction of a nitrile of formula (XV) wherein G¹ is oxygen, with ahydroxylamine as described under 7).

19) Compounds of formula (XV) wherein G¹ is oxygen, can be prepared byreacting an acid derivative of formula (XVI) wherein G¹ is oxygen and Ris OH, C₁-C₆alkoxy or Cl, F or Br, with an amine of formula (III) asdescribed under 1). Compounds of formula (XVI) wherein G¹ is oxygen andR is C₁-C₆alkoxy, such as methoxy or tert-butoxy, are commerciallyavailable or can be made by methods known to a person skilled in theart. Alternatively, compounds of formula (XV) wherein G¹ is oxygen, canbe prepared by displacing the leaving group of a compound of formula(XIII) wherein G¹ is oxygen and X^(B) is a leaving group, for example ahalogen, such as bromo, with a cyano group.

20) Alternatively, compounds of formula (I) wherein G¹ is oxygen, can beprepared by cyclisation of a compound of formula (XX) wherein G¹ isoxygen, as shown in Scheme 5. The cyclisation of a compound of formula(XX) can also be referred to as the dehydration of a compound of formula(XX). Such reactions are usually carried out in the presence of an acid,for example an inorganic acid, such as hydrochloric acid or sulfuricacid, or a sulfonic acid, such as methanesulfonic acid, optionally in asolvent, such as water, ethanol, or tetrahydrofuran, or a mixturethereof. The reaction is carried out at a temperature of from 0° C. to100° C., preferably from 40° C. to 80° C. Representative experimentalconditions for this transformation are described in SyntheticCommunications 2003, 23, 4163-4171. Alternatively, dehydration can becarried out using a dehydrating agent, such as phosphorus pentoxide, ina solvent, such as chloroform, at a temperature of −20° C. to +50°,preferably at 0° C., as described in Journal of Heterocyclic Chemistry1990, 27, 275. Alternatively, cyclisation can be carried out underMitsonobu conditions involving treatment of a compound of formula (XX)with a phosphine, such as triphenylphosphine, and an azodicarboxylatereagent, such as diethyl azodicarboxylate, diisopropyl azodicarboxylateor dicyclohexyl azodicarboxylate, in a solvent, such as tetrahydrofuran,at a temperature of from 0° C. to 80° C., preferably from 0° C. toambient temperature.

21) Compounds of formula (XX), wherein G¹ is oxygen, can be made byreaction of a β-hydroxy ketone of formula (XIX) wherein G¹ is oxygen,with a hydroxylamine as described under 7).

22) Compounds of formula (XIX) wherein G¹ is oxygen, can be made byaldol-type reaction of a methyl ketone of formula (XVIII) wherein G¹ isoxygen, with a ketone of formula (XXI). Such reactions are usuallycarried out in the presence of a base, such as sodium hydride, lithiumhydride, lithium diisopropylamide or lithium hexamethyldisilazide, in asolvent, such as tetrahydrofuran, at a temperature of from −78° C. to+100° C., preferably from 0° C. to +80° C. Alternatively, the reactioncan be performed using a Lewis acid, such as titanium tetrachloride, andan amine, such as triethylamine, diisopropylethylamine,tetramethylethylenediamine (“TMEDA”) or tributylamine, in a solvent,such as dichloromethane, at a temperature of from −78° C. to ambienttemperature, preferably at −78° C. Representative conditions for such atransformation are given in Tetrahedron Letters 1997, 38, 8727-8730.Ketones of formula (XXI) are commercially available or can be made bymethods known to a person skilled in the art.

23) Compounds of formula (XVIII) wherein G¹ is oxygen, can be made byreacting an acid derivative of formula (XVII) wherein G¹ is oxygen and Ris OH, C₁-C₆alkoxy or Cl, F or Br, with an amine of formula (III) asdescribed under 1).

24) Compounds of formula (XVII) wherein G¹ is oxygen and R isC₁-C₆alkoxy, can be prepared by reacting a compound of formula (X)wherein G¹ is oxygen, R is C₁-C₆alkoxy and X^(B) is a leaving group, forexample a halogen, such as bromo, with an acetylating reagent, such astributyl(1-ethoxyvinyl)tin, ethyl vinyl ether or butyl vinyl ether, in apresence of a catalyst, such aspalladium(0)tetrakis(triphenylphosphine), in a solvent, such astetrahydrofuran or toluene, at a temperature of from 60° C. to 110° C.The reaction may afford an intermediate of formula (XVII′) wherein G¹ isoxygen, R is C₁-C₆alkoxy and R′ is C₁-C₆alkyl, which can be hydrolyzedto a compound of formula (XVII). Alternatively, the reaction may yield acompound of formula (XVII) directly.

The hydrolysis of the intermediate of formula (XVII′), if required, isusually carried out in the presence of an acid, such as hydrochloricacid, in a solvent, such as water or ethyl acetate, or a mixturethereof, at a temperature of from 0° C. to 50° C., preferably at ambienttemperature.

25) Alternatively, compounds of formula (XX) wherein G¹ is oxygen, canbe prepared by reacting a methyl oxime of formula (XXII) wherein G¹ isoxygen, with a ketone of formula (XXI) in an aldol-type reaction asshown in Scheme 6. Such reactions are usually carried out by treatingthe methyl oxime of formula (XXII) wherein G¹ is oxygen, with a base,such as butyl lithium, lithium diisopropylamide or lithiumhexamethyldisilazide, in a solvent, such as tetrahydrofuran, at atemperature of from −78° C. to ambient temperature, preferably from −20°C. to 0° C., followed by addition of the ketone of formula (XXI) at atemperature of from −78° C. to 0° C., preferably at 0° C. Representativeconditions for such a transformation can be found in SyntheticCommunications 2003, 23, 4163-4171.

26) Compounds of formula (XXII) wherein G¹ is oxygen, can be made byreaction of a methyl ketone of formula (XVIII) wherein G¹ is oxygen,with a hydroxylamine as described under 7).

27) Alternatively, compounds of formula (I) wherein G¹ is oxygen, can beobtained by reacting an unsaturated ketone of formula (XXIV) wherein G¹is oxygen, with a hydroxylamine, such as hydroxylamine hydrochloride, asshown on Scheme 7. Such reactions can be performed optionally in thepresence of a base, such as sodium hydroxide or potassium hydroxide, ina solvent, such as methanol, ethanol, or water, or a mixture thereof, ata temperature of from 0° C. to 100° C., preferably from ambienttemperature to 80° C. Such conditions are described, for example, in J.Indian Chemical Society 1988, 65(9), 640-2. Such reactions mayoptionally lead to intermediates of formula (XXIV′)

Such intermediates can be converted into compounds of formula (I) in thepresence of an acid, such as hydrochloric acid or acetic acid, or amixture thereof, or a base, such as sodium methoxide, optionally in asolvent, such as methanol or diethyl ether, at a temperature of from 0°C. to 100° C. Representative procedures for this reaction are describedin Eur. J. Org. Chem. 2002, p 1919.

28) Compounds of formula (XXIV) wherein G¹ is oxygen, can be obtained byvarious methods. For example, they can be prepared by reacting in afirst step a compound of formula (XVIII) wherein G¹ is oxygen and Hal isa halogen, such as bromo or chloro, with a phosphine, such astriphenylphosphine. Such reactions are usually performed in a solvent,such as toluene, at a temperature of from ambient temperature to 150°C., preferably from 80° C. to 120° C. In a second step, the intermediateis treated with a ketone of formula (XXI) and a base, such as butyllithium or triethylamine, in a solvent, such as tetrahydrofuran, at atemperature of from −78° C. to +100° C., preferably from ambienttemperature to +80° C. Such conditions are described, for example, inJournal of Organic Chemistry 2006, 71(9), 3545-3550.

29) Compounds of formula (XVIII) wherein G¹ is oxygen and Hal is ahalogen, such as bromo or chloro, can be prepared by reacting a methylketone of formula (XVIII) wherein G¹ is oxygen, with a halogenatingagent, such as bromine or chlorine, in a solvent, such as acetic acid,at a temperature of from 0° C. to 50° C., preferably from ambienttemperature to 40° C.

30) Compounds of formula (VII), (IX), (X), (XVI), (XVII), (XXV) and(XXVI) are either known in the literature or can be made by a numbermethods known to a person skilled in the art. Examples of such methodsare shown on Scheme 8. Thus, a compound of formula (XVI) may be obtainedby cyanation of a compound of formula (X). A compound of formula (IX)may be obtained by oxidation of a compound of formula (XXV). And acompound of formula (VII) may be obtained by oxidation of a compound offormula (XXVI). The preparation of some of these compounds can be foundin the preparation examples.

31) 7-Methyl-1H-benzoimidazole-4-carboxylic acid can be prepared asdescribed in US 2004/0167194.

The compounds of formula (I) can be used to combat and controlinfestations of insect pests such as Lepidoptera, Diptera, Hemiptera,Thysanoptera, Orthoptera, Dictyoptera, Coleoptera, Siphonaptera,Hymenoptera and Isoptera and also other invertebrate pests, for example,acarine, nematode and mollusc pests. Insects, acarines, nematodes andmolluscs are hereinafter collectively referred to as pests. The pestswhich may be combated and controlled by the use of the inventioncompounds include those pests associated with agriculture (which termincludes the growing of crops for food and fiber products), horticultureand animal husbandry, companion animals, forestry and the storage ofproducts of vegetable origin (such as fruit, grain and timber); thosepests associated with the damage of man-made structures and thetransmission of diseases of man and animals; and also nuisance pests(such as flies).

The compounds of the invention may be used for example on turf,ornamentals, such as flowers, shrubs, broad-leaved trees or evergreens,for example conifers, as well as for tree injection, pest management andthe like.

Examples of pest species which may be controlled by the compounds offormula (I) include: Myzus persicae (aphid), Aphis gossypii (aphid),Aphis fabae (aphid), Lygus spp. (capsids), Dysdercus spp. (capsids),Nilaparvata lugens (planthopper), Nephotettixc incticeps (leafhopper),Nezara spp. (stinkbugs), Euschistus spp. (stinkbugs), Leptocorisa spp.(stinkbugs), Frankliniella occidentalis (thrip), Thrips spp. (thrips),Leptinotarsa decemlineata (Colorado potato beetle), Anthonomus grandis(boll weevil), Aonidiella spp. (scale insects), Trialeurodes spp. (whiteflies), Bemisia tabaci (white fly), Ostrinia nubilalis (European cornborer), Spodoptera littoralis (cotton leafworm), Heliothis virescens(tobacco budworm), Helicoverpa armigera (cotton bollworm), Helicoverpazea (cotton bollworm), Sylepta derogata (cotton leaf roller), Pierisbrassicae (white butterfly), Plutella xylostella (diamond back moth),Agrotis spp. (cutworms), Chilo suppressalis (rice stem borer), Locusta.migratoria (locust), Chortiocetes terminifera (locust), Diabrotica spp.(rootworms), Panonychus ulmi (European red mite), Panonychus citri(citrus red mite), Tetranychus urticae (two-spotted spider mite),Tetranychus cinnabarinus (carmine spider mite), Phyllocoptruta oleivora(citrus rust mite), Polyphagotarsonemus latus (broad mite), Brevipalpusspp. (flat mites), Boophilus microplus (cattle tick), Dermacentorvariabilis (American dog tick), Ctenocephalides felis (cat flea),Liriomyza spp. (leafminer), Musca domestica (housefly), Aedes aegypti(mosquito), Anopheles spp. (mosquitoes), Culex spp. (mosquitoes),Lucillia spp. (blowflies), Blattella germanica (cockroach), Periplanetaamericana (cockroach), Blatta orientalis (cockroach), termites of theMastotermitidae (for example Mastotermes spp.), the Kalotermitidae (forexample Neotermes spp.), the Rhinotermitidae (for example Coptotermesformosanus, Reticulitermes flavipes, R. speratu, R. virginicus, R.hesperus, and R. santonensis) and the Termitidae (for exampleGlobitermes sulfureus), Solenopsis geminata (fire ant), Monomoriumpharaonis (pharaoh's ant), Damalinia spp. and Linognathus spp. (bitingand sucking lice), Meloidogyne spp. (root knot nematodes), Globoderaspp. and Heterodera spp. (cyst nematodes), Pratylenchus spp. (lesionnematodes), Rhodopholus spp. (banana burrowing nematodes), Tylenchulusspp. (citrus nematodes), Haemonchus contortus (barber pole worm),Caenorhabditis elegans (vinegar eelworm), Trichostrongylus spp. (gastrointestinal nematodes) and Deroceras reticulatum (slug).

The invention therefore provides a method of combating and controllinginsects, acarines, nematodes or molluscs which comprises applying aninsecticidally, acaricidally, nematicidally or molluscicidally effectiveamount of a compound of formula (I), or a composition containing acompound of formula (I), to a pest, a locus of pest, preferably a plant,or to a plant susceptible to attack by a pest, The compounds of formula(I) are preferably used against insects, acarines or nematodes.

The invention provides a method of combating and/or controlling insects,acarines, nematodes or molluscs which comprises applying aninsecticidally, acaricidally, nematicidally or molluscicidally effectiveamount of a compound of formula (I), or a composition containing acompound of formula (I), to a pest, a locus of pest, preferably a plant,or to a plant susceptible to attack by a pest, The compounds of formula(I) are preferably used against insects, acarines or nematodes.

The term “plant” as used herein includes seedlings, bushes and trees.

Crops are to be understood as also including those crops which have beenrendered tolerant to herbicides or classes of herbicides (e.g. ALS-,GS-, EPSPS-, PPO- and HPPD-inhibitors) by conventional methods ofbreeding or by genetic engineering. An example of a crop that has beenrendered tolerant to imidazolinones, e.g. imazamox, by conventionalmethods of breeding is Clearfield® summer rape (canola). Examples ofcrops that have been rendered tolerant to herbicides by geneticengineering methods include e.g. glyphosate- and glufosinate-resistantmaize varieties commercially available under the trade namesRoundupReady® and LibertyLink®.

Crops are also to be understood as being those which have been renderedresistant to harmful insects by genetic engineering methods, for exampleBt maize (resistant to European corn borer), Bt cotton (resistant tocotton boll weevil) and also Bt potatoes (resistant to Colorado beetle).Examples of Bt maize are the Bt 176 maize hybrids of NK® (SyngentaSeeds). Examples of transgenic plants comprising one or more genes thatcode for an insecticidal resistance and express one or more toxins areKnockOut® (maize), Yield Gard® (maize), NuCOTIN33B® (cotton), Bollgard®(cotton), NewLeaf® (potatoes), NatureGard® and Protexcta®.

Plant crops or seed material thereof can be both resistant to herbicidesand, at the same time, resistant to insect feeding (“stacked” transgenicevents). For example, seed can have the ability to express aninsecticidal Cry3 protein while at the same time being tolerant toglyphosate.

Crops are also to be understood as being those which are obtained byconventional methods of breeding or genetic engineering and containso-called output traits (e.g. improved storage stability, highernutritional value and improved flavor).

In order to apply a compound of formula (I) as an insecticide,acaricide, nematicide or molluscicide to a pest, a locus of pest, or toa plant susceptible to attack by a pest, a compound of formula (I) isusually formulated into a composition which includes, in addition to thecompound of formula (I), a suitable inert diluent or carrier and,optionally, a surface active agent (SFA). SFAs are chemicals which areable to modify the properties of an interface (for example,liquid/solid, liquid/air or liquid/liquid interfaces) by lowering theinterfacial tension and thereby leading to changes in other properties(for example dispersion, emulsification and wetting). It is preferredthat all compositions (both solid and liquid formulations) comprise, byweight, 0.0001 to 95%, more preferably 1 to 85%, for example 5 to 60%,of a compound of formula (I). The composition is generally used for thecontrol of pests such that a compound of formula (I) is applied at arate of from 0.1 g to 10 kg per hectare, preferably from 1 g to 6 kg perhectare, more preferably from 1 g to 1 kg per hectare.

When used in a seed dressing, a compound of formula (I) is used at arate of 0.0001 g to 10 g (for example 0.001 g or 0.05 g), preferably0.005 g to 10 g, more preferably 0.005 g to 4 g, per kilogram of seed.

In another aspect the present invention provides an insecticidal,acaricidal, nematicidal or molluscicidal composition comprising aninsecticidally, acaricidally, nematicidally or molluscicidally effectiveamount of a compound of formula (I) and a suitable carrier or diluenttherefor. The composition is preferably an insecticidal, acaricidal,nematicidal or molluscicidal composition.

The compositions can be chosen from a number of formulation types,including dustable powders (DP), soluble powders (SP), water solublegranules (SG), water dispersible granules (WG), wettable powders (WP),granules (GR) (slow or fast release), soluble concentrates (SL), oilmiscible liquids (OL), ultra low volume liquids (UL), emulsifiableconcentrates (EC), dispersible concentrates (DC), emulsions (both oil inwater (EW) and water in oil (EO)), micro-emulsions (ME), suspensionconcentrates (SC), aerosols, fogging/smoke formulations, capsulesuspensions (CS) and seed treatment formulations. The formulation typechosen in any instance will depend upon the particular purpose envisagedand the physical, chemical and biological properties of the compound offormula (I).

Dustable powders (DP) may be prepared by mixing a compound of formula(I) with one or more solid diluents (for example natural clays, kaolin,pyrophyllite, bentonite, alumina, montmorillonite, kieselguhr, chalk,diatomaceous earths, calcium phosphates, calcium and magnesiumcarbonates, sulfur, lime, flours, talc and other organic and inorganicsolid carriers) and mechanically grinding the mixture to a fine powder.

Soluble powders (SP) may be prepared by mixing a compound of formula (I)with one or more water-soluble inorganic salts (such as sodiumbicarbonate, sodium carbonate or magnesium sulfate) or one or morewater-soluble organic solids (such as a polysaccharide) and, optionally,one or more wetting agents, one or more dispersing agents or a mixtureof said agents to improve water dispersibility/solubility. The mixtureis then ground to a fine powder. Similar compositions may also begranulated to form water soluble granules (SG).

Wettable powders (WP) may be prepared by mixing a compound of formula(I) with one or more solid diluents or carriers, one or more wettingagents and, preferably, one or more dispersing agents and, optionally,one or more suspending agents to facilitate the dispersion in liquids.The mixture is then ground to a fine powder. Similar compositions mayalso be granulated to form water dispersible granules (WG).

Granules (GR) may be formed either by granulating a mixture of acompound of formula (I) and one or more powdered solid diluents orcarriers, or from pre-formed blank granules by absorbing a compound offormula (I) (or a solution thereof, in a suitable agent) in a porousgranular material (such as pumice, attapulgite clays, fuller's earth,kieselguhr, diatomaceous earths or ground corn cobs) or by adsorbing acompound of formula (I) (or a solution thereof, in a suitable agent) onto a hard core material (such as sands, silicates, mineral carbonates,sulfates or phosphates) and drying if necessary. Agents which arecommonly used to aid absorption or adsorption include solvents (such asaliphatic and aromatic petroleum solvents, alcohols, ethers, ketones andesters) and sticking agents (such as polyvinyl acetates, polyvinylalcohols, dextrins, sugars and vegetable oils). One or more otheradditives may also be included in granules (for example an emulsifyingagent, wetting agent or dispersing agent).

Dispersible Concentrates (DC) may be prepared by dissolving a compoundof formula (I) in water or an organic solvent, such as a ketone, alcoholor glycol ether. These solutions may contain a surface active agent (forexample to improve water dilution or prevent crystallization in a spraytank).

Emulsifiable concentrates (EC) or oil-in-water emulsions (EW) may beprepared by dissolving a compound of formula (I) in an organic solvent(optionally containing one or more wetting agents, one or moreemulsifying agents or a mixture of said agents). Suitable organicsolvents for use in ECs include aromatic hydrocarbons (such asalkylbenzenes or alkylnaphthalenes, exemplified by SOLVESSO 100,SOLVESSO 150 and SOLVESSO 200; SOLVESSO is a Registered Trade Mark),ketones (such as cyclohexanone or methylcyclohexanone) and alcohols(such as benzyl alcohol, furfuryl alcohol or butanol),N-alkylpyrrolidones (such as N-methylpyrrolidone or N-octylpyrrolidone),dimethyl amides of fatty acids (such as C₈-C₁₀ fatty acid dimethylamide)and chlorinated hydrocarbons. An EC product may spontaneously emulsifyon addition to water, to produce an emulsion with sufficient stabilityto allow spray application through appropriate equipment. Preparation ofan EW involves obtaining a compound of formula (I) either as a liquid(if it is not a liquid at room temperature, it may be melted at areasonable temperature, typically below 70° C.) or in solution (bydissolving it in an appropriate solvent) and then emulsifiying theresultant liquid or solution into water containing one or more SFAs,under high shear, to produce an emulsion. Suitable solvents for use inEWs include vegetable oils, chlorinated hydrocarbons (such aschlorobenzenes), aromatic solvents (such as alkylbenzenes oralkylnaphthalenes) and other appropriate organic solvents which have alow solubility in water.

Microemulsions (ME) may be prepared by mixing water with a blend of oneor more solvents with one or more SFAs, to produce spontaneously athermodynamically stable isotropic liquid formulation. A compound offormula (I) is present initially in either the water or the solvent/SFAblend. Suitable solvents for use in MEs include those hereinbeforedescribed for use in ECs or in EWs. An ME may be either an oil-in-wateror a water-in-oil system (which system is present may be determined byconductivity measurements) and may be suitable for mixing water-solubleand oil-soluble pesticides in the same formulation. An ME is suitablefor dilution into water, either remaining as a microemulsion or forminga conventional oil-in-water emulsion.

Suspension concentrates (SC) may comprise aqueous or non-aqueoussuspensions of finely divided insoluble solid particles of a compound offormula (I). SCs may be prepared by ball or bead milling the solidcompound of formula (I) in a suitable medium, optionally with one ormore dispersing agents, to produce a fine particle suspension of thecompound. One or more wetting agents may be included in the compositionand a suspending agent may be included to reduce the rate at which theparticles settle. Alternatively, a compound of formula (I) may be drymilled and added to water, containing agents hereinbefore described, toproduce the desired end product.

Aerosol formulations comprise a compound of formula (I) and a suitablepropellant (for example n-butane). A compound of formula (I) may also bedissolved or dispersed in a suitable medium (for example water or awater miscible liquid, such as n-propanol) to provide compositions foruse in non-pressurized, hand-actuated spray pumps.

A compound of formula (I) may be mixed in the dry state with apyrotechnic mixture to form a composition suitable for generating, in anenclosed space, a smoke containing the compound.

Capsule suspensions (CS) may be prepared in a manner similar to thepreparation of EW formulations but with an additional polymerizationstage such that an aqueous dispersion of oil droplets is obtained, inwhich each oil droplet is encapsulated by a polymeric shell and containsa compound of formula (I) and, optionally, a carrier or diluenttherefor. The polymeric shell may be produced by either an interfacialpolycondensation reaction or by a coacervation procedure. Thecompositions may provide for controlled release of the compound offormula (I) and they may be used for seed treatment. A compound offormula (I) may also be formulated in a biodegradable polymeric matrixto provide a slow, controlled release of the compound.

A composition may include one or more additives to improve thebiological performance of the composition (for example by improvingwetting, retention or distribution on surfaces; resistance to rain ontreated surfaces; or uptake or mobility of a compound of formula (I)).Such additives include surface active agents, spray additives based onoils, for example certain mineral oils or natural plant oils (such assoy bean and rape seed oil), and blends of these with otherbio-enhancing adjuvants (ingredients which may aid or modify the actionof a compound of formula (I)).

A compound of formula (I) may also be formulated for use as a seedtreatment, for example as a powder composition, including a powder fordry seed treatment (DS), a water soluble powder (SS) or a waterdispersible powder for slurry treatment (WS), or as a liquidcomposition, including a flowable concentrate (FS), a solution (LS) or acapsule suspension (CS). The preparations of DS, SS, WS, FS and LScompositions are very similar to those of, respectively, DP, SP, WP, SCand DC compositions described above. Compositions for treating seed mayinclude an agent for assisting the adhesion of the composition to theseed (for example a mineral oil or a film-forming barrier).

Wetting agents, dispersing agents and emulsifying agents may be surfaceSFAs of the cationic, anionic, amphoteric or non-ionic type.

Suitable SFAs of the cationic type include quaternary ammonium compounds(for example cetyltrimethyl ammonium bromide), imidazolines and aminesalts.

Suitable anionic SFAs include alkali metals salts of fatty acids, saltsof aliphatic monoesters of sulfuric acid (for example sodium laurylsulfate), salts of sulfonated aromatic compounds (for example sodiumdodecylbenzenesulfonate, calcium dodecylbenzenesulfonate,butylnaphthalene sulfonate and mixtures of sodium di-isopropyl- andtri-isopropyl-naphthalene sulfonates), ether sulfates, alcohol ethersulfates (for example sodium laureth-3-sulfate), ether carboxylates (forexample sodium laureth-3-carboxylate), phosphate esters (products fromthe reaction between one or more fatty alcohols and phosphoric acid(predominately mono-esters) or phosphorus pentoxide (predominatelydi-esters), for example the reaction between lauryl alcohol andtetraphosphoric acid; additionally these products may be ethoxylated),sulfosuccinamates, paraffin or olefine sulfonates, taurates andlignosulfonates.

Suitable SFAs of the amphoteric type include betaines, propionates andglycinates.

Suitable SFAs of the non-ionic type include condensation products ofalkylene oxides, such as ethylene oxide, propylene oxide, butylene oxideor mixtures thereof, with fatty alcohols (such as oleyl alcohol or cetylalcohol) or with alkylphenols (such as octylphenol, nonylphenol oroctylcresol); partial esters derived from long chain fatty acids orhexitol anhydrides; condensation products of said partial esters withethylene oxide; block polymers (comprising ethylene oxide and propyleneoxide); alkanolamides; simple esters (for example fatty acidpolyethylene glycol esters); amine oxides (for example lauryl dimethylamine oxide); and lecithins.

Suitable suspending agents include hydrophilic colloids (such aspolysaccharides, polyvinylpyrrolidone or sodium carboxymethylcellulose)and swelling clays (such as bentonite or attapulgite).

A compound of formula (I) may be applied by any of the known means ofapplying pesticidal compounds. For example, it may be applied,formulated or unformulated, to the pests or to a locus of the pests(such as a habitat of the pests, or a growing plant liable toinfestation by the pests) or to any part of the plant, including thefoliage, stems, branches or roots, to the seed before it is planted orto other media in which plants are growing or are to be planted (such assoil surrounding the roots, the soil generally, paddy water orhydroponic culture systems), directly or it may be sprayed on, dustedon, applied by dipping, applied as a cream or paste formulation, appliedas a vapor or applied through distribution or incorporation of acomposition (such as a granular composition or a composition packed in awater-soluble bag) in soil or an aqueous environment.

A compound of formula (I) may also be injected into plants or sprayedonto vegetation using electrodynamic spraying techniques or other lowvolume methods, or applied by land or aerial irrigation systems.

Compositions for use as aqueous preparations (aqueous solutions ordispersions) are generally supplied in the form of a concentratecontaining a high proportion of the active ingredient, the concentratebeing added to water before use. These concentrates, which may includeDCs, SCs, ECs, EWs, MEs, SGs, SPs, WPs, WGs and CSs, are often requiredto withstand storage for prolonged periods and, after such storage, tobe capable of addition to water to form aqueous preparations whichremain homogeneous for a sufficient time to enable them to be applied byconventional spray equipment. Such aqueous preparations may containvarying amounts of a compound of formula (I) (for example 0.0001 to 10%,by weight) depending upon the purpose for which they are to be used.

A compound of formula (I) may be used in mixtures with fertilizers (forexample nitrogen-, potassium- or phosphorus-containing fertilizers).Suitable formulation types include granules of fertilizer. The mixturespreferably contain up to 25% by weight of the compound of formula (I).

The invention therefore also provides a fertilizer compositioncomprising a fertilizer and a compound of formula (I).

The compositions of this invention may contain other compounds havingbiological activity, for example micronutrients or compounds havingfungicidal activity or which possess plant growth regulating,herbicidal, insecticidal, nematicidal or acaricidal activity.

The compound of formula (I) may be the sole active ingredient of thecomposition or it may be admixed with one or more additional activeingredients such as a pesticide, fungicide, synergist, herbicide orplant growth regulator where appropriate. An additional activeingredient may: provide a composition having a broader spectrum ofactivity or increased persistence at a locus; synergize the activity orcomplement the activity (for example by increasing the speed of effector overcoming repellency) of the compound of formula (I); or help toovercome or prevent the development of resistance to individualcomponents. The particular additional active ingredient will depend uponthe intended utility of the composition. Examples of suitable pesticidesinclude the following:

a) Pyrethroids, such as permethrin, cypermethrin, fenvalerate,esfenvalerate, deltamethrin, cyhalothrin (in particularlambda-cyhalothrin), bifenthrin, fenpropathrin, cyfluthrin, tefluthrin,fish safe pyrethroids (for example ethofenprox), natural pyrethrin,tetramethrin, s-bioallethrin, fenfluthrin, prallethrin or5-benzyl-3-furylmethyl-(E)-(1R,3S)-2,2-dimethyl-3-(2-oxothiolan-3-ylidenemethyl)cyclopropanecarboxylate;b) Organophosphates, such as, profenofos, sulprofos, acephate, methylparathion, azinphos-methyl, demeton-s-methyl, heptenophos, thiometon,fenamiphos, monocrotophos, profenofos, triazophos, methamidophos,dimethoate, phosphamidon, malathion, chlorpyrifos, phosalone, terbufos,fensulfothion, fonofos, phorate, phoxim, pirimiphos-methyl,pirimiphos-ethyl, fenitrothion, fosthiazate or diazinon;c) Carbamates (including aryl carbamates), such as pirimicarb,triazamate, cloethocarb, carbofuran, furathiocarb, ethiofencarb,aldicarb, thiofurox, carbosulfan, bendiocarb, fenobucarb, propoxur,methomyl or oxamyl;d) Benzoyl ureas, such as diflubenzuron, triflumuron, hexaflumuron,flufenoxuron or chlorfluazuron;e) Organic tin compounds, such as cyhexatin, fenbutatin oxide orazocyclotin;f) Pyrazoles, such as tebufenpyrad and fenpyroximate;g) Macrolides, such as avermectins or milbemycins, for exampleabamectin, emamectin benzoate, ivermectin, milbemycin, spinosad orazadirachtin;h) Hormones or pheromones;i) Organochlorine compounds such as endosulfan, benzene hexachloride,DDT, chlordane or dieldrin;j) Amidines, such as chlordimeform or amitraz;k) Fumigant agents, such as chloropicrin, dichloropropane, methylbromide or metam;l) Neonicotinoid compounds such as imidacloprid, thiacloprid,acetamiprid, nitenpyram, dinotefuran or thiamethoxam;m) Diacylhydrazines, such as tebufenozide, chromafenozide ormethoxyfenozide;n) Diphenyl ethers, such as diofenolan or pyriproxifen;o) Indoxacarb;p) Chlorfenapyr;q) Pymetrozine;r) Spirotetramat, spirodiclofen or spiromesifen; ors) Flubendiamid or rynaxypyr

In addition to the major chemical classes of pesticide listed above,other pesticides having particular targets may be employed in thecomposition, if appropriate for the intended utility of the composition.For instance, selective insecticides for particular crops, for examplestemborer specific insecticides (such as cartap) or hopper specificinsecticides (such as buprofezin) for use in rice may be employed.Alternatively insecticides or acaricides specific for particular insectspecies/stages may also be included in the compositions (for exampleacaricidal ovo-larvicides, such as clofentezine, flubenzimine,hexythiazox or tetradifon; acaricidal motilicides, such as dicofol orpropargite; acaricides, such as bromopropylate or chlorobenzilate; orgrowth regulators, such as hydramethylnon, cyromazine, methoprene,chlorfluazuron or diflubenzuron).

Examples of fungicidal compounds which may be included in thecomposition of the invention are(E)-N-methyl-2-[2-(2,5-dimethylphenoxymethyl)phenyl]-2-methoxy-iminoacetamide(SSF-129),4-bromo-2-cyano-N,N-dimethyl-6-trifluoromethyl-benzimidazole-1-sulfonamide,a-[N-(3-chloro-2,6-xylyl)-2-methoxyacetamido]-γ-butyrolactone,4-chloro-2-cyano-N,N-dimethyl-5-p-tolylimidazole-1-sulfonamide (IKF-916,cyamidazosulfamid),3-5-dichloro-N-(3-chloro-1-ethyl-1-methyl-2-oxopropyl)-4-methylbenzamide(RH-7281, zoxamide),N-allyl-4,5,-dimethyl-2-trimethylsilylthiophene-3-carboxamide(MON65500),N-(1-cyano-1,2-dimethylpropyl)-2-(2,4-dichlorophenoxy)propionamide(AC382042), N-(2-methoxy-5-pyridyl)-cyclopropane carboxamide,acibenzolar (CGA245704), alanycarb, aldimorph, anilazine, azaconazole,azoxystrobin, benalaxyl, benomyl, biloxazol, bitertanol, blasticidin S,bromuconazole, bupirimate, captafol, captan, carbendazim, carbendazimchlorhydrate, carboxin, carpropamid, carvone, CGA41396, CGA41397,chinomethionate, chlorothalonil, chlorozolinate, clozylacon, coppercontaining compounds such as copper oxychloride, copper oxyquinolate,copper sulfate, copper tallate and Bordeaux mixture, cymoxanil,cyproconazole, cyprodinil, debacarb, di-2-pyridyl disulfide1,1′-dioxide, dichlofluanid, diclomezine, dicloran, diethofencarb,difenoconazole, difenzoquat, diflumetorim, O,O-di-iso-propyl-5-benzylthiophosphate, dimefluazole, dimetconazole, dimethomorph, dimethirimol,diniconazole, dinocap, dithianon, dodecyl dimethyl ammonium chloride,dodemorph, dodine, doguadine, edifenphos, epoxiconazole, ethirimol,ethyl-(Z)—N-benzyl-N([methyl(methyl-thioethylideneaminooxycarbonyl)amino]thio)-β-alaninate,etridiazole, famoxadone, fenamidone (RPA407213), fenarimol,fenbuconazole, fenfuram, fenhexamid (KBR2738), fenpiclonil, fenpropidin,fenpropimorph, fentin acetate, fentin hydroxide, ferbam, ferimzone,fluazinam, fludioxonil, flumetover, fluoroimide, fluquinconazole,flusilazole, flutolanil, flutriafol, folpet, fuberidazole, furalaxyl,furametpyr, guazatine, hexaconazole, hydroxyisoxazole, hymexazole,imazalil, imibenconazole, iminoctadine, iminoctadine triacetate,ipconazole, iprobenfos, iprodione, iprovalicarb (SZX0722), isopropanylbutyl carbamate, isoprothiolane, kasugamycin, kresoxim-methyl, LY186054,LY211795, LY248908, mancozeb, maneb, mefenoxam, mepanipyrim, mepronil,metalaxyl, metconazole, metiram, metiram-zinc, metominostrobin,myclobutanil, neoasozin, nickel dimethyldithiocarbamate,nitrothal-isopropyl, nuarimol, ofurace, organomercury compounds,oxadixyl, oxasulfuron, oxolinic acid, oxpoconazole, oxycarboxin,pefurazoate, penconazole, pencycuron, phenazin oxide, phosetyl-A1,phosphorus acids, phthalide, picoxystrobin (ZA1963), polyoxin D,polyram, probenazole, prochloraz, procymidone, propamocarb,propiconazole, propineb, propionic acid, pyrazophos, pyrifenox,pyrimethanil, pyroquilon, pyroxyfur, pyrrolnitrin, quaternary ammoniumcompounds, quinomethionate, quinoxyfen, quintozene, sipconazole (F-155),sodium pentachlorophenate, spiroxamine, streptomycin, sulfur,tebuconazole, tecloftalam, tecnazene, tetraconazole, thiabendazole,thifluzamid, 2-(thiocyanomethylthio)benzothiazole, thiophanate-methyl,thiram, timibenconazole, tolclofos-methyl, tolylfluanid, triadimefon,triadimenol, triazbutil, triazoxide, tricyclazole, tridemorph,trifloxystrobin (CGA279202), triforine, triflumizole, triticonazole,validamycin A, vapam, vinclozolin, zineb and ziram.

The compounds of formula (I) may be mixed with soil, peat or otherrooting media for the protection of plants against seed-borne,soil-borne or foliar fungal diseases.

Examples of suitable synergists for use in the compositions includepiperonyl butoxide, sesamex, safroxan and dodecyl imidazole.

Suitable herbicides and plant-growth regulators for inclusion in thecompositions will depend upon the intended target and the effectrequired.

An example of a rice selective herbicide which may be included ispropanil. An example of a plant growth regulator for use in cotton isPIX™

Some mixtures may comprise active ingredients which have significantlydifferent physical, chemical or biological properties such that they donot easily lend themselves to the same conventional formulation type. Inthese circumstances other formulation types may be prepared. Forexample, where one active ingredient is a water insoluble solid and theother a water insoluble liquid, it may nevertheless be possible todisperse each active ingredient in the same continuous aqueous phase bydispersing the solid active ingredient as a suspension (using apreparation analogous to that of an SC) but dispersing the liquid activeingredient as an emulsion (using a preparation analogous to that of anEW). The resultant composition is a suspoemulsion (SE) formulation.

The following Examples illustrate, but do not limit, the invention.

Preparation Examples

The following abbreviations were used throughout this section:s=singlet; bs=broad singlet; d=doublet; dd=double doublet; dt=doubletriplet; t=triplet, tt=triple triplet, q=quartet, sept=septet;m=multiplet; Me=methyl; Et=ethyl; Pr=propyl; Bu=butyl.

Example I1.1 Preparation of4-bromo-7-bromomethyl-benzo[1,2,5]thiadiazole

Bromine (9.78 ml) was added to a solution of4-methylbenzo[c][1,2,5]thiadiazole (commercially available) (15 g) inaqueous hydrobromic acid (48%) (100 ml). The reaction mixture was heatedat reflux temperature for 2 hours. The reaction mixture was allowed tocool to ambient temperature and diluted with aqueous sodiummetabisulfite (20 g in 250 ml water). The mixture was extracted twicewith dichloromethane. The combined organic phases were washed with waterand brine, dried over sodium sulfate, and concentrated to give a mixtureof brominated products. This mixture was suspended inα,α,α-trifluorotoluene (250 ml) and N-bromosuccinimide (“NBS”) (13.88 g)and 2,2′-azobis(2-methylpropionitrile) (“AIBN”) (0.640 g) were added.The reaction mixture was heated at 90° C. for 3 hours. The reactionmixture was allowed to cool to ambient temperature and was diluted withdichloromethane (600 ml) and aqueous hydrochloric acid (1M) (300 ml).The phases were separated and the organic layer was washed successivelywith aqueous hydrochloric acid (1M) (2×250 ml), water (200 ml) and brine(200 ml), dried over sodium sulfate and concentrated to give4-bromo-7-bromomethyl-benzo[1,2,5]thiadiazole (29.05 g) as a yellowsolid. ¹H-NMR (400 MHz, CDCl₃): 7.82 (d, 1H), 7.54 (d, 1H), 4.94 (s, 2H)ppm.

Example I1.2 Preparation of(7-bromo-benzo[1,2,5]thiadiazol-4-yl)-methanol

A mixture of 4-bromo-7-bromomethyl-benzo[1,2,5]thiadiazole (29.05 g)(Example II), potassium carbonate (65.2 g) and water (400 ml) wasstirred at 110° C. for 16 hours. The reaction mixture was cooled toambient temperature and quenched by addition of aqueous hydrochloricacid (2M) (400 ml). Ethyl acetate (600 ml) was added to the mixture. Thephases were separated and the organic layer was washed successively withaqueous hydrochloric acid (2M) (400 ml), water (250 ml) and brine (250ml), dried over sodium sulfate and concentrated to give(7-bromo-benzo[1,2,5]thiadiazol-4-yl)-methanol (20.22 g) as a orangesolid. ¹H-NMR (400 MHz, CDCl₃): 7.87 (d, 1H), 7.57 (d, 1H), 5.14 (s, 2H)ppm.

Example I1.3 Preparation of7-bromo-benzo[1,2,5]thiadiazole-4-carbaldehyde

To a solution of (7-bromo-benzo[1,2,5]thiadiazol-4-yl)-methanol (20.22g) (Example I2) in dichloromethane (185 ml) was added manganese(IV)oxide (71.7 g). The suspension was stirred at ambient temperature for 16hours. The reaction mixture was filtered through a plug of Celite®. Thefiltrate was concentrated to give7-bromo-benzo[1,2,5]thiadiazole-4-carbaldehyde (16.65 g) as an orangesolid. ¹H-NMR (400 MHz, CDCl₃): 10.74 (s, 1H), 8.11-8.05 (m, 2H) ppm.

Example I1.4 Preparation of7-bromo-benzo[1,2,5]thiadiazole-4-carbaldehyde oxime

To a solution of 7-bromo-benzo[1,2,5]thiadiazole-4-carbaldehyde (16.65g) (Example I3) in ethanol (150 ml) were added hydroxylaminehydrochloride (9.52 g), sodium hydrogen carbonate (11.51 g) and water(15 ml). The reaction mixture was stirred at ambient temperature for 16hours. The reaction mixture was diluted with ethyl acetate (1500 ml) andwater (400 ml). After separation of the phases, the aqueous layer wasextracted with ethyl acetate (200 ml). The combined organic layers werewashed with water (200 ml) and brine (200 ml), dried over sodium sulfateand concentrated to give 7-bromo-benzo[1,2,5]-thiadiazole-4-carbaldehydeoxime (16.65 g) as a brown solid. ¹H-NMR (DMSO-d6, 400 MHz): 11.94 (s,1H), 8.66 (s, 1H), 8.09-9.90 (m, 2H) ppm.

Example I1.5 Preparation of7-bromo-N-hydroxybenzo[1,2,5]thiadiazole-4-carbimidoyl chloride

To a solution of 7-bromo-benzo[1,2,5]thiadiazole-4-carbaldehyde oxime(16.65 g) (Example I4) in N,N-dimethylformamide (150 ml) was addedN-chlorosuccinimide (“NCS”) (10.34 g). The reaction mixture stirred atambient temperature for 16 hours. Water (750 ml) was added to thereaction mixture and the resulting solid was isolated by filtration toobtain 7-bromo-N-hydroxybenzo[1,2,5]thiadiazole-4-carbimidoyl chloride(15.77 g) as a yellow solid which was used without further purification.

Example I1.6 Preparation of4-bromo-7-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-benzo[1,2,5]thiadiazole

To a solution of 7-bromo-N-hydroxybenzo[1,2,5]thiadiazole-4-carbimidoylchloride (10.01 g) (Example I5) in 2-propanol (140 ml) was added1,3-dichloro-5-(3,3,3-trifluoroprop-1-en-2-yl)benzene (6.87 g) (preparedaccording to WO 2005/085216) and sodium hydrogen carbonate (5.99 g). Thereaction mixture was stirred at 65° C. for 3 hours. The reaction mixturewas concentrated and the residue was purified by column chromatography(heptane/ethyl acetate 9:1) to give4-bromo-7-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-benzo[1,2,5]thiadiazole(7.4 g). ¹H-NMR (DMSO-d6, 400 MHz): 8.17-7.53 (m, 5H), 4.70 (d, 1H),4.49 (d, 1H) ppm.

Example I1.7 Preparation of7-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-benzo[1,2,5]thiadiazole-4-carboxylicacid methyl ester

Triethylamine (7.8 ml) and methanol (72 ml) were added at ambienttemperature to a solution of4-bromo-7-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-benzo[1,2,5]thiadiazole(7.96 g) (Example I6) in N,N-dimethylformamide (72 ml).[1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II)(“PdCl₂(dppf)”) (654 mg) was added and the reaction mixture was stirredin a pressure reactor in an atmosphere of carbon monoxide (3 bar) at 87°C. for 16 hours. The reaction mixture was cooled to ambient temperature,filtered through a plug of Celite® and concentrated. The residue waspurified by column chromatography (heptane/ethyl acetate) to give7-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-benzo[1,2,5]thiadiazole-4-carboxylicacid methyl ester (4.01 g) as an orange oil. ¹H-NMR (CDCl₃, 400 MHz):8.43-7.57 (m, 5H), 4.66 (d, 1H), 4.27 (d, 1H), 4.09 (s, 3H) ppm.

Example I1.8 Preparation of7-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-benzo[1,2,5]thiadiazole-4-carboxylicacid

To a solution of7-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-isoxazol-3-yl]-benzo[1,2,5]thiadiazole-4-carboxylicacid methyl ester (4.01 g) (Example I7) in tetrahydrofuran (30 ml) wasadded aqueous sodium hydroxide (1M) (25.3 ml). The reaction mixture wasstirred at ambient temperature for 1.5 hours. Aqueous hydrochloric acid(1M) (100 ml) was added and the mixture diluted with ethyl acetate (150ml). After separation of the layers, the aqueous layer was extractedwith ethyl acetate (2×75 ml). The combined organic layers were washedwith water (75 ml) and brine (75 ml), dried over sodium sulfate andconcentrated. The residue was purified by column chromatography(dichloromethane/methanol) to give7-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-benzo[1,2,5]thiadiazole-4-carboxylicacid (1.29 g) as yellow solid. ¹H-NMR (DMSO-d6, 400 MHz): 13.67 (bs,1H), 8.37-7.26 (m, 5H), 4.76 (d, 1H), 4.53 (d, 1H) ppm.

Example P1 General Method for Preparing the Compounds of the Inventionin Parallel

To a solution of7-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-benzo[1,2,5]thiadiazole-4-carboxylicacid (30 μmol) (Example I8) in N,N-dimethyl-acetamide (“DMA”) (0.4 ml)was added successively a solution of an amine of formula HNR¹R² (30μmol) in N,N-dimethylacetamide (“DMA”) (0.145 ml), diisopropylethylamine(Hunig's Base) (0.02 ml, 100 μmol), and a solution ofbis(2-oxo-3-oxazolidinyl)phosphonic chloride (“BOP-Cl”) (15.3 mg) inN,N-dimethylacetamide (“DMA”) (0.2 ml). The reaction mixture was stirredat 80° C. for 16 hours. Then the reaction mixture was diluted withacetonitrile (0.6 ml) and a sample was used for LC-MS analysis. Theremaining mixture was further diluted withacetonitrile/N,N-dimethylformamide (4:1) (0.8 ml) and purified by HPLC.This method was used to prepare a number of compounds (Compound Nos. A1to A24 of Table A) in parallel.

The following method was used for HPLC-MS analysis:

Method (Agilent 1100er Series) with the following HPLC gradientconditions (Solvent A: 0.1% of formic acid in water; Solvent B: 0.1% offormic acid in acetonitrile.

Time (minutes) A (%) B (%) Flow rate (ml/min) 0 80 20 1.7 2.5 0 100 1.72.8 0 100 1.7 2.9 80 20 1.7

Type of column: Waters atlantis dc18; Column length: 20 mm; Internaldiameter of column: 3 mm; Particle Size: 3 micron; Temperature: 40° C.

The characteristic values obtained for each compound were the retentiontime (“RT”, recorded in minutes) and the molecular ion, typically thecation MH⁺ as listed in Table A.

TABLE A Compounds of formula (Ia): (Ia)

Comp No. R¹ R² RT (min) MH⁺ A1 butyl- H 4.29 517 A22,2,2-trifluoroethyl- H 4.07 543 A3 ethyl- H 3.84 489 A41-methoxy-prop-2-yl- H 3.95 533 A5 (1H-benzimidazol-2-yl)- H 2.78 591methyl- A6 3,3,3-trifluoropropyl- H 4.11 557 A7 but-2-yl- H 4.25 517 A8(tetrahydro-furan-2-yl)- H 3.85 545 methyl- A9 phenyl-methyl- H 4.23 551A10 (2-fluoro-phenyl)-methyl- H 4.32 569 A11 1-phenyl-eth-1-yl- H 4.44565 A12 (4-methoxy-phenyl)-methyl- H 4.25 581 A13 1-oxo-thietan-3-yl- H3.18 5.49 A14 (2-chloro-pyrid-5-yl)-methyl- H 3.98 586 A153-fluoro-phenyl- H 4.57 555 A16 4-(N,N-dimethylamino- H 4.29 644sulfonyl)-phenyl- A17 1,3-dimethyl-1H-pyrazol-5-yl- H 3.80 555 A184-methyl-thiazol-2-yl- H 4.30 558 A19 3-methyl-thietan-3-yl- H 4.31 547A20 2-methyl-1-methylthio-prop-2- H 4.48 563 yl- A211,1-dioxo-thietan-3-yl- H 5.52 564 A22 thietan-3-yl- H 4.05 533 A23bicyclo[2.2.1]heptan-2-yl- H 4.62 555 A24 cyclobutyl- H 4.19 515

Example I2.1 Preparation of 1-amino-4-bromo-6-methy-2-nitrobenzoic acid

A mixture of 4-bromo-1-(formyl-amino)-6-methyl-2-nitrobenzoic acid (20g) (prepared according to US 2004/0167194 A1), concentrated hydrochloricacid (50 ml), and water (150 ml) was heated at 50° C. for 16 h. Thereaction mixture was cooled to room temperature, treated ice cold water,and extracted with ethyl acetate (3×50 ml). The combined organic layerswere dried over sodium sulfate and concentrated to give1-amino-4-bromo-6-methyl-2-nitrobenzoic acid (16 g). ¹H-NMR (400 MHz,CDCl₃): 13.53 (bs, 1H), 7.56 (s, 1H), 7.07 (bs, 2H), 2.20 (s, 3H). LCMS:m/z=272.89 (M−H).

Example I2.2 Preparation of 1,2-diamino-6-methylbenzoic acid

A suspension of 1-amino-4-bromo-6-methyl-2-nitrobenzoic acid (16 g) andPd/C (3.2 g) in methanol (400 ml) was stirred under hydrogen (1 bar) for48 h and filtered through Celite under nitrogen atmosphere. Evaporationof methanol and purification by chromatography (hexane/ethyl acetate40:60) gave 1,2-diamino-6-methylbenzoic acid (6.7 g) as a brown solid(6.7 g). ¹H-NMR (400 MHz, CDCl₃): 12.09 (bs, 1H), 6.73 (d, 1H), 6.13 (d,1H), 1.98 (s, 3H). LCMS: m/z=167.11 (M+H)

Example I2.3 Preparation of 4-methylbenzotriazole-7-carboxylic acid

A solution of 1,2-diamino-6-methylbenzoic acid (6.7 g) in concentratedhydrochloric acid (40 ml) was cooled to 0° C., treated with sodiumnitrite (2.7 g) portion wise, and stirred for 2 h. The reaction mixturewas quenched with water (100 ml) and extracted with ethyl acetate (3×50ml). The combined organic layers were dried over sodium sulfate andconcentrated to give 4-methylbenzotriazole-7-carboxylic acid (5 g).¹H-NMR (400 MHz, DMSO): 15.77 (bs, 1H), 13.30 (bs, 1H), 7.97 (d, 1H),7.27 (d, 1H), 2.76 (s, 3H). LCMS: m/z=178.09 (M+H).

Example I2.4 Preparation of 1,4-dimethylbenzotriazole-7-carboxylic acidmethyl ester and 2,4-dimethylbenzotriazole-7-carboxylic acid methylester

A solution of 4-methylbenzotriazole-7-carboxylic acid (0.1 g) indimethyl formamide (20 ml) was treated with cesium carbonate (0.37 g)and methyl iodide (0.1 ml) stirred at 50° C. for 5 h. The reactionmixture was quenched with water (10 ml) and extracted with ethyl acetate(3×5 ml). The combined organic layers were dried over sodium sulfate andconcentrated. Chromatographic purification (hexane/ethyl acetate 85:15)gave 1,4-dimethylbenzotriazole-7-carboxylic acid methyl ester (30 mg)and 2,4-dimethylbenzotriazole-7-carboxylic acid methyl ester (26 mg).

1,4-Dimethylbenzotriazole-7-carboxylic acid methyl ester

¹H-NMR (400 MHz, CDCl₃): 8.03 (d, 1H), 7.15 (dd, 1H), 4.57 (s, 3H), 3.97(s, 3H), 2.81 (d, 3H). LCMS: m/z=206.03 (M+H).

2,4-Dimethylbenzotriazole-7-carboxylic acid methyl ester

¹H-NMR (400 MHz, CDCl₃): 8.07 (d, 1H), 7.21 (dd, 1H), 4.59 (s, 3H), 4.02(s, 3H), 2.72 (d, 3H). LCMS: m/z=206.03 (M+H).

Example I2.5 Preparation of 4-formyl-1-methylbenzotriazole-7-carboxylicacid methyl ester

A solution of 1,4-dimethylbenzotriazole-7-carboxylic acid methyl ester(0.1 g) in carbontetrachloride (10 ml) was treated withN-bromosuccinimide (0.5 g) and benzoyl peroxide (20 mg) and heated at80° C. for 72 h under nitrogen atmosphere. The reaction mixture wascooled, filtered through Celite, and concentrated. The crude product(0.15 g) was directly used in the next step.

The crude product from above was dissolved in 2:1 mixture ofacetone/water (6 ml), treated with silver nitrate (0.175 g), and stirredin dark condition for 16 h. The reaction mixture was concentrated toremove acetone and extracted with ethyl acetate (3×10 ml). The combinedorganic layers were dried over sodium sulfate and concentrated.Chromatographic purification (hexane/ethyl acetate 15:85) gave4-formyl-1-methylbenzotriazole-7-carboxylic acid methyl ester (0.05 g)as a white solid. ¹H-NMR (400 MHz, CDCl₃): 10.55 (s, 1H), 8.28 (d, 1H),8.04 (d, 1H), 4.69 (s, 3H), 4.08 (s, 3H), 2.77 (s, 3H). GC-MS: m/z=219(M).

Example I2.6 Preparation of 4-formyl-2-methylbenzotriazole-7-carboxylicacid methyl ester

2,4-Dimethylbenzotriazole-7-carboxylic acid methyl ester (0.1 g) wasconverted to 4-formyl-2-methylbenzotriazole-7-carboxylic acid methylester (51 mg) using the same procedure as in Example I13. ¹H-NMR (400MHz, CDCl₃): 11.041 (d, 1H), 8.2 (d, 1H), 7.96 (d, 1H), 4.63 (s, 3H),4.04 (s, 3H), 2.77 (s, 3H). LC-MS: m/z=220 (M+H).

Example I2.7 Preparation of1-methyl-6-methoxycarbonylbenzotriazole-4-carbaldehyde oxime

A solution of 4-formyl-1-methylbenzotriazole-7-carboxylic acid methylester (0.15 g) in isopropyl alcohol (10 ml) and water (5 ml) was treatedwith hydroxylamine hydrochloride (0.05 g) and sodium acetate (0.06 g)and stirred for 2 h. Isopropyl alcohol was removed and the remainingmixture was extracted with ethyl acetate (3×5 ml). The combined organiclayers were dried over sodium sulfate and concentrated to give1-methyl-6-methoxycarbonylbenzotriazole-4-carbaldehyde oxime (0.14 g).¹H-NMR (400 MHz, DMSO): 12.06 (s, 1H), 8.55 (s, 1H), 8.11 (d, 1H), 7.79(d, 1H), 4.57 (s, 3H), 3.93 (s, 3H). LC-MS: m/z=235.08 (M+H).

Example I2.8 Preparation of2-methyl-6-methoxycarbonylbenzotriazole-4-carbaldehyde oxime

4-Formyl-2-methylbenzotriazole-7-carboxylic acid methyl ester (0.15 g)was converted to 2-methyl-6-methoxycarbonylbenzotriazole-4-carbaldehydeoxime (0.142 g) using the same procedure as in Example I15. ¹H-NMR (400MHz, DMSO): 12.06 (s, 1H), 8.55 (s, 1H), 8.11 (d, 1H), 7.79 (d, 1H),4.57 (s, 3H), 3.93 (s, 3H). LC-MS: m/z=235.06 (M+H).

Example I2.9 Preparation of3-methyl-4-methoxycarbonyl-7-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-benzotriazole

A solution of 1-methyl-6-methoxycarbonylbenzotriazole-4-carbaldehydeoxime (0.1 g) in dimethyl formamide (10 ml) was treated withN-chlorosuccinimide (0.17 g) and stirred at 40° C. for 2 h undernitrogen atmosphere. Then reaction mixture was cooled to roomtemperature and treated with1,3-dichloro-5-(3,3,3-trifluoroprop-1-en-2-yl)benzene (0.47 g) (preparedaccording to WO 2005/085216) and triethylamine (0.02 ml), stirred atroom temperature for 16 h under nitrogen atmosphere, and treated withwater (50 ml). The mixture was extracted with ethyl acetate (3×10 ml)and the combined organic layers were dried over sodium sulfate.Evaporation of solvents and purification by column chromatograph gave3-methyl-4-methoxycarbonyl-7-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-benzotriazole(85 mg). ¹H-NMR (400 MHz, CDCl₃): 8.15 (d, 1H), 8.05 (d, 1H), 7.58 (d,2H), 7.42 (t, 1H), 4.74 (bd, 1H), 4.60 (s, 1H), 4.38 (bd, 1H), 4.02 (s,3H). LC-MS: m/z=472.96 (M+H).

Example I2.10 Preparation of2-methyl-4-methoxycarbonyl-7-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-benzotriazole

2-Methyl-6-methoxycarbonylbenzotriazole-4-carbaldehyde oxime (0.1 g) wasconverted to2-methyl-4-methoxycarbonyl-7-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-benzotriazole(750 mg) using the same procedure as in Example I17. ¹H-NMR (400 MHz,CDCl₃): 8.18 (d, 1H), 7.94 (d, 1H), 7.56 (d, 2H), 7.43 (t, 1H), 4.66 (s,1H), 4.50 (bd, 1H), 4.07 (s, 3H). LC-MS: m/z=472.99 (M+H).

Example I2.11 Preparation of3-methyl-7-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-benzotriazole-4-carboxylicacid

A solution of3-methyl-4-methoxycarbonyl-7-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-benzotriazole(0.1 g), lithiumhydroxide (11 mg) in tetrahydrofuran (10 ml) and water(5 ml) was stirred for 30 minutes. Tetrahydrofuran was removed andextracted with ethyl acetate (3×5 ml). The combined organic layers weredried over sodium sulfate and concentrated to give3-methyl-7-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-benzotriazole-4-carboxylicacid. ¹H-NMR (400 MHz, DMSO): 7.80 (t, 1H), 7.73 (d, 1H), 7.69 (d, 1H),7.62 (d, 1H), 4.74 (bd, 1H), 4.50 (s, 3H), 4.46 (bd, 1H). LC-MS:m/z=458.98 (M+H).

Example I2.12 Preparation of2-methyl-7-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-benzotriazole-4-carboxylicacid

2-Methyl-4-methoxycarbonyl-7-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-benzotriazole(0.1 g) was converted to2-methyl-7-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-benzotriazole-4-carboxylicacid (81 mg) using the same procedure as in Example I19. ¹H-NMR (400MHz, DMSO): 13.53 (bs, 1H), 8.10 (m, 1H), 7.88 (d, 1H), 7.81 (t, 1H),7.69 (m, 2H), 4.64 (d, 1H), 4.61 (s, 3H), 4.44 (d, 1H).

Example P2.1 General Method for Preparing the Compounds of the Inventionin Parallel

Oxalyl chloride (0.2 ml) was added drop wise to a solution of3-methyl-7-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-benzotriazole-4-carboxylicacid (0.1 g) in tetrahydrofuran (5 ml) and 1 drop ofN,N-dimethylformamide and stirred at room temperature under nitrogenatmosphere for 4 h. The mixture was concentrated and dissolved intetrahydrofuran (10 ml), treated with an amine of formula HNR¹R² (2equivalents), triethylamine (1 equivalent) and stirred for 16 h undernitrogen atmosphere. The reaction mixture was concentrated and purifiedby chromatography. This method was used to prepare a number ofcompounds.

Example P2.2 General Method for Preparing the Compounds of the Inventionin Parallel

2-methyl-7-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-benzotriazole-4-carboxylicacid was converted to a number of compounds of type if according to theprocedure as in Example P2.1.

The following method was used for HPLC-MS analysis:

Method (Agilent 1200er Series) with the following HPLC gradientconditions (Solvent A: 0.1% of formic acid in water; Solvent B: 0.1% offormic acid in acetonitrile).

Time (minutes) A (%) B (%) Flow rate (ml/min) 0 90 10 1.0 7.0 5 95 1.07.5 0 100 1.0 12.0 0 100 1.0Type of column: Eclipse (XBD-c18) Column length: 150 mm; Internaldiameter of column: 4.5 mm; Particle Size: 5 micron; Temperature: 40° C.

The characteristic values obtained for each compound were the retentiontime (“RT”, recorded in minutes) and the molecular ion, typically thecation MH⁺ as listed in Tables B and C.

TABLE B Compounds of formula (Ie): (Ie)

Comp No. R¹ R² RT (min) MH⁺ B1 butyl- H 4.75 514 B22,2,2-trifluoroethyl- H 4.70 540 B3 cyclobutyl- H 4.68 512

TABLE C Compounds of formula (If): (If)

Comp No. R¹ R² RT (min) MH⁺ C1 butyl- H 4.84 514 C22,2,2-trifluoroethyl- H 4.72 540 C3 thietan-3-yl- H 4.78 530 C4cyclobutyl- H 4.77 512

Example I3.1 Preparation of 3,4-dimethyl-2-nitrobenzoic acid

A solution of 3,4-dimethylbenzoic acid (40 g) in concentrated sulphuricacid (250 ml) was cooled to 0° C., treated with a solution of potassiumnitrite (27 g) in sulphuric acid (100 ml) dropwise over a period of 1 h,and stirred for 2 h. The reaction mixture was quenched with ice cooledwater (100 ml). The solid precipitated was filtered, dissolved in water(2 l), basified with 2N aqueous sodium hydroxide. The solution wasacidified to pH 4 with 2N aqueous hydrochloric acid and filtered to get3,4-dimethyl-5-nitrobenzoic acid (II) (25 g) as colorless solid. Thefiltrate was further acidified to pH 3 and filtered get3,4-dimethyl-2-nitrobenzoic acid (I) (13 g) as colorless solid.

3,4-dimethyl-2-nitrobenzoic acid (I): ¹H-NMR (400 MHz, CDCl₃): 2.11 (s,3H), 2.49 (s, 3H), 7.51 (d, 1H), 7.97 (d, 1H), 7.76 (d, 1H).

3,4-dimethyl-5-nitrobenzoic acid (II): ¹H-NMR (400 MHz, CDCl₃): 2.72 (s,6H), 7.50 (s, 1H), 7.76 (s, 1H).

Example I3.2 Preparation of methyl 3,4-dimethyl-2-nitrobenzoate

A solution of 3,4-dimethyl-2-nitrobenzoic acid (13 g) and thionylchloride (11.8 g) in toluene (100 ml) was refluxed for 4 h. The reactionmixture was cooled at 0° C., treated with methanol (15 ml) and thesolvent was removed under vacuum. The reaction mixture was treated water(50 ml) and extracted with ethyl acetate (3×50 ml). The combined organiclayers were dried over sodium sulfate and concentrated to give methyl3,4-dimethyl-2-nitrobenzoate (10 g). ¹H-NMR (400 MHz, CDCl₃): 2.19 (s,3H), 2.38 (s, 3H), 3.87 (s, 3H), 7.25 (d, 1H), 7.79 (d, 1H).

Example I3.3 Preparation of methyl 3,4-dimethyl-2-aminobenzoate

A suspension of methyl 3,4-dimethyl-2-nitrobenzoate (23 g) and Pd/C (2.3g) in methanol (400 ml) was stirred under hydrogen (1 bar) for 48 h andfiltered through Celite under nitrogen atmosphere. Evaporation ofmethanol gave methyl 3,4-dimethyl-2-aminobenzoate (20 g). ¹H-NMR (400MHz, CDCl₃): 7.67 (d, 1H), 6.6 (d, 1H), 3.86 (s, 3H), 2.27 (s, 3H), 2.1(s, 3H).

Example I3.4 Preparation of 4-methyl-1H-indazole-7-carboxylic acidmethyl ester

A solution of methyl 3,4-dimethyl-2-aminobenzoate (10 g) in concentratedhydrochloric acid (20 ml) was cooled to 0° C., treated with solution oftetrafluoroammoniumborate (9.4 g) in water (2 ml), a solution of sodiumnitrite (7.7 g) in water (2 ml) dropwise, stirred for 2 h, filtered toget a solid. The solid residue was dissolved in chloroform (50 m),treated with potassium acetate (2 mol equivalents) and catalytic amountsof 18-Crown-6, and stirred for 12 h. The reaction mixture was treatedwith water (50 ml) and extracted with chloroform (2×50 ml). The combinedorganic layers were dried over sodium sulfate and concentrated.Chromatographic purification (hexane/ethyl acetate 80:20) gave 4-methyl-1H-indazole-7-carboxylic acid methyl ester (3.2 g). ¹H-NMR (400 MHz,CDCl₃): 2.68 (s, 3H), 4.00 (s, 3H), 7.02 (d, 1H), 7.97 (d, 1H), 8.15 (s,1H). LC-MS (methanol): m/z=191 (M+H).

Example I3.5 Preparation of 1,4-dimethyl-1H-indazole-7-carboxyl acidmethyl ester

A solution of 4-methyl-1H-indazole-7-carboxylic acid methyl ester (6 g)in acetonitrile (100 ml) was treated with cesium carbonate (21 g) andmethyl iodide (4.9 ml) and stirred at 50° C. for 8 h. The reactionmixture was concentrated, treated with water (10 ml), and extracted withethyl acetate (3×50 ml). The combined organic layers were dried oversodium sulfate and concentrated. Chromatographic purification(hexane/ethyl acetate 90:10) gave 1,4-dimethyl-1H-indazole-7-carboxylacid methyl ester (4.2 g). ¹H-NMR (400 MHz, CDCl₃): 2.62 (s, 3H), 3.96(s, 3H), 4.27 (s, 3H), 6.92 (d, 1H), 7.87 (d, 1H), 8.05 (s, 1H).

Example I3.6 Preparation of 4-formyl-1-methyl-1H-indazole-7-carboxylicacid methyl ester

A solution of 1,4-dimethyl-1H-indazole-7-carboxyl acid methyl ester (4.2g) in carbontetrachloride (100 ml) was treated with N-bromosuccinimide(14.4 g) and benzoyl peroxide (110 mg) and heated at 90° C. for 16 hunder nitrogen atmosphere. The reaction mixture was cooled, filteredthrough Celite, and concentrated. The crude product (10 g) was directlyused in the next step. The crude product was dissolved in 2:1 mixture ofacetone/water (100 ml), treated with silver nitrate (8.5 g), and stirredin dark condition for 12 h. The reaction mixture was concentrated toremove acetone and extracted with ethyl acetate (3×50 ml). The combinedorganic layers were dried over sodium sulfate and concentrated.Chromatographic purification (hexane/ethyl acetate 10:90) gave4-formyl-1-methyl-1H-indazole-7-carboxylic acid methyl ester (1.5 g) asa white solid. ¹H-NMR (400 MHz, CDCl₃): 10.26 (s, 1H), 8.72 (s, 1H),7.68 (d, 1H), 7.25 (d, 1H), 4.26 (s, 1H), 4.03 (s, 3H). LC-MS(methanol): m/z=219 (M+H).

Example I3.7 Preparation of4-(hydroxyimino-methyl-1-methyl-1H-indazole-7-carboxylic acid methylester

A solution of 4-formyl-1-methyl-1H-indazole-7-carboxylic acid methylester (1.4 g) in isopropyl alcohol (30 ml) and water (20 ml) was treatedwith hydroxylamine hydrochloride (0.62 g) and sodium acetate (0.72 g)and stirred for 4 h. Isopropyl alcohol was removed and the remainingmixture was extracted with ethyl acetate (2×50 ml). The combined organiclayers were dried over sodium sulfate and concentrated to give4-(hydroxyimino-methyl-1-methyl-1H-indazole-7-carboxylic acid methylester (1.5 g). ¹H-NMR (400 MHz, DMSO): 10.1 (s, 1H), 8.5 (s, 1H), 8.4(s, 1H), 7.8 (d, 1H), 7.1 (d, 1H), 4.20 (s, 3H), 4.00 (s, 3H).

Example I3.8 Preparation of4-[5-(3,5-dichlotophenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-1-methyl-1H-indazole-7-carboxylicacid methyl ester]

A solution of 4-(hydroxyimino-methyl-1-methyl-1H-indazole-7-carboxylicacid methyl ester (1.4 g) in dimethyl formamide (50 ml) was treated withN-chlorosuccinimide (0.85 g) and stirred at 50° C. for 3 h undernitrogen atmosphere. Then reaction mixture was cooled to roomtemperature and treated with1,3-dichloro-5-(3,3,3-trifluoroprop-1-en-2-yl)benzene (1.43 g) (preparedaccording to WO 2005/085216) and triethylamine (0.8 ml), stirred at roomtemperature for 16 h under nitrogen atmosphere, and treated with water(50 ml). The solid appeared was filtered and purified by columnchromatograph (hexane/ethyl acetate 20:80) to give4-[5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-1-methyl-1H-indazole-7-carboxylicacid methyl ester (1.1 g). ¹H-NMR (400 MHz, DMSO): 8.47 (s, 1H), 7.95(d, 1H), 7.82 (d, 1H), 7.68 (s, 2H), 7.51 (d, 1H), 4.52 (dd, 2H), 4.09(s, 3H), 3.97 (s, 3H). LC-MS (methanol): m/z=471 (M+H).

Example I3.9 Preparation of4-[5-(3,5-dichlotophenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-1-methyl-1H-indazole-7-carboxylicacid

A solution of4-[5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-1-methyl-1H-indazole-7-carboxylicacid methyl ester (0.7 g), lithiumhydroxide (93 mg) in tetrahydrofuran(20 ml) and water (10 ml) was stirred for 1 h. Tetrahydrofuran wasremoved, and the residue was treated with 2N aqueous hydrochloric acidto get a solid precipitate. Filtration and drying gave4-[5-(3,5-dichlotophenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-1-methyl-1H-indazole-7-carboxylicacid as white solid. ¹H-NMR (400 MHz, DMSO): 8.45 (s, 1H), 7.92 (d, 1H),7.80 (s, 1H), 7.68 (s, 2H), 7.49 (d, 1H), 4.51 (dd, 2H), 4.18 (s, 3H).LC-MS (methanol): m/z=457.87 (M+H).

Example P3 General Method for Preparing the Compounds of the Inventionin Parallel

Oxalyl chloride (0.2 ml) was added drop wise to a solution of4-[5-(3,5-dichlotophenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-1-methyl-1H-indazole-7-carboxylicacid (0.1 g) in tetrahydrofuran (5 ml) and 1 drop ofN,N-dimethylformamide and stirred at room temperature under nitrogenatmosphere for 4-6 h. The mixture was concentrated and dissolved intetrahydrofuran (10 ml), treated with an amine of formula HNR¹R² (2equivalents), triethylamine (1 equivalent) and stirred for 16 h undernitrogen atmosphere. The reaction mixture was concentrated and purifiedby chromatography. This method was used to prepare a number ofcompounds.

TABLE D Compounds of formula (Ig): (Ig)

Comp No. R¹ R² NMR data D1 thietan-3-yl- H ¹H-NMR (400 MHz, CDCl₃): 8.50(d, 1H), 7.55 (s, 2H), 7.44 (s, 1H), 7.34 (d, 1H), 7.02 (d, 1H), 6.74(d, 1H), 5.49 (m, 1H), 4.20 (d, 1H), 4.08 (s, 3H), 3.81 (d, 1H), 3.50(m, 4H). LC-MS (methanol): m/z = 526.81 (M + H). D2 cyclobutyl- H ¹H-NMR(400 MHz, DMSO): 9.06 (s, 1H), 8.39 (s, 1H), 7.82 (s, 1H), 7.69 (s, 2H),7.50 (d, 1H), 7.46 (d, 1H), 4.46 (m, 3H), 4.03 (s, 3H), 2.29 (m, 2H),2.06 (m, 2H), 1.71 (m, 2H). LC-MS (methanol): m/z = 510.98 (M + H).

Example I4.1 Preparation of 3-hydroxy-2-nitro-benzoic acid methyl ester

3-Hydroxy-2-nitro-benzoic acid (commercially available) (31.5 g) wassuspended in acetonitrile (100 ml). Oxalyl chloride (22 ml) inacetonitrile (20 ml) was added dropwise upon which a vigorous gas streamevolved. After 15 minutes the reaction slowed down and therefore, thereaction mixture was heated with a warm water bath (40° C.) for 40minutes. The mixture was concentrated and the residue was re-dissolvedin dichloromethane (100 ml). A mixture of methanol (50 ml) andtriethylamine (20 ml) in dichloromethane (30 ml) was added dropwisewhile cooling the mixture with an ice bath. The reaction mixture wasstirred at ambient temperature for 16 hours. The mixture wasconcentrated and the residue was purified by column chromatography onsilica gel (eluent: 10-55% v/v ethyl acetate in heptane) to give3-hydroxy-2-nitro-benzoic acid methyl ester (15.9 g). 1H-NMR (400 MHz,CDCl₃): 10.15 (bs, 1H), 7.60 (t, 1H), 7.27 (d, 1H), 7.08 (d, 1H), 3.93(s, 3H) ppm.

Example I4.2 Preparation of 4-bromo-3-hydroxy-2-nitro-benzoic acidmethyl ester

To a solution of 3-hydroxy-2-nitrobenzoic acid methyl ester (11 g) inchloroform (220 ml) was added dropwise bromine (18.7 g). The reactionmixture was heated at reflux for 16 hours. The reaction mixture wasallowed to cool to ambient temperature and the reaction quenched byaddition of aqueous sodium metabisulfite (22 g in 100 ml water) and themixture was stirred for 15 minutes. The phases were separated and theorganic phase was washed with brine, dried over sodium sulfate andconcentrated. The residue was crystallized from diethyl ether/heptane togive 4-bromo-3-hydroxy-2-nitro-benzoic acid methyl ester (6.6 g). 1H-NMR(400 MHz, CDCl₃): 9.92 (s, 1H), 7.84 (d, 1H), 7.09 (d, 1H), 3.93 (s, 3H)ppm.

Example I4.3 Preparation of 2-amino-4-bromo-3-hydroxy-benzoic acidmethyl ester

To a solution of 4-bromo-3-hydroxy-2-nitro-benzoic acid methyl ester(3.13 g) in tetrahydrofuran (40 ml) was added a solution of sodiumdithionite (10.23 g) in water (40 ml).

The reaction mixture was stirred at 60° C. for 2 hours. Then thereaction was diluted with ethyl acetate (80 ml) and aqueous hydrochloricacid (1M) (30 ml) and the mixture vigorously shaken. The phases wereseparated and the aqueous phase was extracted with ethyl acetate (60ml). The combined organic extracts were washed with brine, dried oversodium sulfate and concentrated to give2-amino-4-bromo-3-hydroxy-benzoic acid methyl ester (2.46 g). 1H-NMR(400 MHz, CDCl₃): 7.35 (d, 1H), 6.72 (d, 1H), 6.05 (s, 1H), 5.47 (s,1H), 3.87 (s, 3H) ppm.

Example I4.4 Preparation of7-bromo-2-methyl-benzo[d]oxazole-4-carboxylic acid methyl ester

To a solution of 2-amino-4-bromo-3-hydroxy-benzoic acid methyl ester(2.46 g) in toluene (250 ml) was added sequentially triethylamine (1.53ml), pyridinium p-toluenesulfonate (“PPTS”) (0.75 g) and acetyl chloride(0.78 ml). The reaction mixture was heated at reflux for 16 hours. Thereaction mixture was cooled to ambient temperature and diluted withaqueous hydrochloric acid (1M) (100 ml) and ethyl acetate (200 ml). Thephases were separated and the organic extract was washed with aqueoushydrochloric acid (1M) (150 ml) and brine (150 ml) and then dried oversodium sulfate. The solids were removed by filtration and the filtratewas concentrated to give 7-bromo-2 methyl-benzo[d]oxazole-4-carboxylicacid methyl ester (2.94 g). 1H-NMR (400 MHz, CDCl₃): 7.87 (d, 1H), 7.52(d, 1H), 4.04 (s, 3H), 2.77 (s, 3H) ppm.

Example I4.5 Preparation of(7-bromo-2-methyl-benzo[d]oxazol-4-yl)-methanol

To a solution of 7-bromo-2 methyl-benzo[d]oxazole-4-carboxylic acidmethyl ester (8.64 g) in tetrahydrofuran (250 ml) was added dropwise asolution of diisobutylaluminium hydride (“DIBAL-H”) (1M in hexane) (80ml) under a nitrogen atmosphere at 0° C. The reaction mixture wasstirred at 0° C. for 20 minutes. Then the ice-bath was removed and thereaction mixture was allowed to warm to ambient temperature. After 40minutes the mixture was cooled with an ice-bath and the reaction wasquenched by the slow addition of water (5.0 ml). The mixture was pouredonto aqueous sodium hydrogen carbonate (saturated) (300 ml) andextracted with diethyl ether (400 ml). The aqueous phase was furtherextracted with diethyl ether (2×300 ml). The combined organic extractswere washed with brine, dried over sodium sulfate and concentrated. Theresidue was triturated in a mixture of diisopropyl ether and heptane(3:1) to give (7-bromo-2-methyl-benzo[d]oxazol-4-yl)-methanol (4.45 g).1H-NMR (400 MHz, CDCl₃): 7.41 (d, 1H), 7.17 (d, 1H), 4.98 (s, 3H), 3.06(s, 1H), 2.67 (s, 3H) ppm.

Example I4.6 Preparation of7-bromo-2-methyl-benzo[d]oxazole-4-carbaldehyde

To a solution of (7-bromo-2-methyl-benzo[d]oxazol-4-yl) methanol (5.16g) in dichloromethane (300 ml) was added manganese(IV) oxide (59.9 g)and the suspension stirred at ambient temperature for 16 hours. Thereaction mixture was filtered through a plug of silica gel and thefiltrate concentrated to give7-bromo-2-methyl-benzo[d]oxazole-4-carbaldehyde (3.23 g). LC-MS:R_(T)=1.83 min, [M+H]⁺=240.0/242.0, using the following method:

Method (Agilent 1100er Series) with the following HPLC gradientconditions (Solvent A: 0.05% formic acid in water; Solvent B: 0.04%formic acid in acetonitrile).

Time (minutes) A (%) B (%) Flow (ml/min) 0.0 95 5.0 1.7 2.0 0.0 100 1.72.8 0.0 100 1.7 2.9 95 5.0 1.7Type of column: Phenomenex Gemini C18; Column length: 30 mm, Internaldiameter of column 3 mm, Particle size 3 micron; Temperature 60° C.

The characteristics obtained for each compound were the retention time(“RT” recorded in minutes) and the molecular ion MH⁺.

Example I4.7 Preparation of(E)-7-bromo-2-methyl-benzo[d]oxazole-4-carbaldehyde oxime

To a suspension of 7-bromo-2-methyl-benzo[d]oxazole-4-carbaldehyde (3.23g) in a mixture of methanol and water (7:3) (60 ml) were addedsuccessively hydroxylamine hydrochloride (1.03 g) and triethylamine(2.06 ml) and the reaction mixture was stirred at ambient temperaturefor 1 hour. The reaction mixture was diluted with ethyl acetate (200 ml)and water (200 ml). The phases were separated and the aqueous phase wasextracted with ethyl acetate (150 ml). The combined organic extractswere washed with brine (200 ml), dried over sodium sulfate andconcentrated to give (E)-7-bromo-2-methyl-benzo[d]oxazole-4-carbaldehydeoxime (3.61 g) as a brown solid. 1H-NMR (400 MHz, CDCl₃): 9.47 (s, 1H)7.47 (d, 1H), 7.33 (d, 1H), 2.74 (s, 3H) ppm.

Example I4.8 Preparation of(Z)-7-bromo-N-hydroxy-2-methyl-benzo[d]oxazole-4-carbimidoyl chloride

To a solution of (E)-7-bromo-2-methyl-benzo[d]oxazole-4-carbaldehydeoxime (3.61 g) in dimethylformamide (30 ml) was added N-bromosuccinimide(“NCS”) (7.54 g) and the reaction mixture stirred at ambient temperaturefor two hours. Water (300 ml) was added to the mixture and the solidswere isolated by filtration to give(Z)-7-bromo-N-hydroxy-2-methyl-benzo[d]oxazole-4-carbimidoyl chloride(3.63 g) as an orange solid. 1H-NMR (DMSO-d6, 400 MHz): 12.76 (s, 1H)7.69 (d, 1H), 7.58 (d, 1H), 2.68 (s, 3H) ppm.

Example I4.9 Preparation of7-bromo-4-(5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl)-2-methyl-benzo[d]oxazole

To a solution of7-bromo-N-hydroxy-2-methyl-benzo[d]oxazole-4-carbimidoyl chloride (3.63g) in 2-propanol (100 ml) was added1,3-dichloro-5-(1-trifluoromethyl-vinyl)-benzene (preparation describedin, for example, EP 1,731,512) (3.43 g) and sodium hydrogen carbonate(1.44 g). The reaction mixture was stirred at 65° C. for 16 hours. Thereaction mixture was concentrated and the residue was purified by columnchromatography on silica gel (eluent: 2-25% v/v ethyl acetate inheptane) to give7-bromo-4-(5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl)-2-methyl-benzo[d]oxazole(3.7 g). 1H-NMR (400 MHz, CDCl₃): 7.71-7.42 (m, 5H), 4.50 (d, 1H), 4.06(d, 1H), 2.73 (s, 3H) ppm.

Example I4.10 Preparation of4-(5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl)-2-methyl-benzo[d]oxazole-7-carboxylicacid methyl ester

To a solution of7-bromo-4-(5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl)-2-methyl-benzo[d]oxazole(3.5 g) in dimethylformamide (40 ml) was added successivelytriethylamine (2.5 ml), methanol (60 ml) and[1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II)(“PdC12(dppf)”) (259 mg). The reaction mixture was stirred in a pressurereactor in an atmosphere of carbon monoxide (4 bar) at 80° C. for 16hours. The reaction mixture was cooled to ambient temperature, filteredover a plug of Celite® and concentrated. The residue was purified bycolumn chromatography on silica gel (eluent: 15-55% v/v ethyl acetate inheptane) to give4-(5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl)-2-methyl-benzo[d]oxazole-7-carboxylicacid methyl ester (2.75 g). 1H-NMR (400 MHz, CDCl₃): 7.95-7.42 (m, 5H),4.56 (d, 1H), 4.12 (d, 1H), 4.02 (s, 3H), 2.77 (s, 3H) ppm.

Example I4.11 Preparation of4-(5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl)-2-methyl-benzo[d]oxazole-7-carboxylicacid

To a solution of4-(5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl)-2-methyl-benzo[d]oxazole-7-carboxylicacid methyl ester (2.75 g) in tetrahydrofuran (50 ml) was added aqueoussodium hydroxide (1M) (8.7 ml) and methanol (5 ml). The reaction mixturewas stirred at ambient temperature for 2.5 hours. The reaction mixturewas diluted with aqueous hydrochloric acid (1M) (150 ml) and ethylacetate (200 ml) and the phases separated. The organic phase was washedwith brine, dried over sodium sulfate and concentrated. The residue waspurified by column chromatography on silica gel (eluent: 1-6% v/vmethanol in dichloromethane) to give4-(5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl)-2-methyl-benzo[d]oxazole-7-carboxylicacid (2.12 g) as yellow solid. 1H-NMR (400 MHz, CDCl₃): 8.05-7.43 (m,5H), 4.57 (d, 1H), 4.13 (d, 1H), 2.79 (s, 3H) ppm.

Example P4 General Method for Preparing the Compounds of the Inventionin Parallel

To a solution of the carboxylic acid (30 μmol) in dimethylacetamide (0.4ml) was added a solution of the amine (30 μmol) in dimethylacetamide(0.145 ml) followed by diisopropylethylamine (Hunig's Base) (0.02 ml,100 μmol) and a solution of bis(2-oxo-3-oxazolidinyl)phosphonic chloride(“BOP-Cl”) (15.3 mg) in dimethylacetamide (0.2 ml). The reaction mixturewas stirred at 80° C. for 16 hours. Then the mixture was diluted withacetonitrile (0.6 ml) and a sample was used for the LC-MS analysis. Theremaining mixture was further diluted withacetonitrile/dimethylformamide (4:1) (0.8 ml) and purified by HPLC togive the desired compound.

The following method was used for HPLC-MS analysis:

Method (Agilent 1100er Series) with the following HPLC gradientconditions (Solvent A: 0.1% formic acid in water; Solvent B: 0.1% formicacid in acetonitrile).

Time (minutes) A (%) B (%) Flow (ml/min) 0.0 90 10 1.7 5.5 0.0 100 1.75.8 0.0 100 1.7 5.9 90 10 1.7Type of column: Waters Atlantis dc18; Column length: 20 mm, Internaldiameter of column 3 mm, Particle size 3 micron; Temperature 40° C.

The characteristics obtained for each compound were the retention time(“RT” recorded in minutes) and the molecular io, typically the cationMH⁺ as listed in Table E.

TABLE E Compounds of formula Ih Ih

Comp No. R¹ R² RT (min) MH⁺ E1

H 3.47 562 E2

H 4.12 544 E3

H 3.18 546 E4

H 3.91 530

Biological Examples

This Example illustrates the pesticidal/insecticidal properties ofcompounds of formula (I). Tests were performed as follows:

Spodoptera littoralis (Egyptian cotton leafworm):

Cotton leaf discs were placed on agar in a 24-well microtiter plate andsprayed with test solutions at an application rate of 200 ppm. Afterdrying, the leaf discs were infested with 5 L1 larvae. The samples werechecked for mortality, feeding behavior, and growth regulation 3 daysafter treatment (DAT).

The following compound gave at least 80% control of Spodopteralittoralis: A2, A3, A5, A6, A13, A19, A20, A22, A24.

Heliothis virescens (Tobacco budworm):

Eggs (0-24 h old) were placed in 24-well microtiter plate on artificialdiet and treated with test solutions at an application rate of 200 ppm(concentration in well 18 ppm) by pipetting. After an incubation periodof 4 days, samples were checked for egg mortality, larval mortality, andgrowth regulation.

The following compound gave at least 80% control of Heliothis virescens:A12, A13, A21, A22, A24.

Plutella xylostella (Diamond back moth):

24-well microtiter plate (MTP) with artificial diet was treated withtest solutions at an application rate of 200 ppm (concentration in well18 ppm) by pipetting. After drying, the MTP's were infested with L2larvae (7-12 per well). After an incubation period of 6 days, sampleswere checked for larval mortality and growth regulation.

The following compound gave at least 80% control of Plutella xylostella:A1, A2, A3, A4, A5, A6.

Diabrotica balteata (Corn root worm):

A 24-well microtiter plate (MTP) with artificial diet was treated withtest solutions at an application rate of 200 ppm (concentration in well18 ppm) by pipetting. After drying, the MTP's were infested with L2larvae (6-10 per well). After an incubation period of 5 days, sampleswere checked for larval mortality and growth regulation.

The following compound gave at least 80% control of Diabrotica balteata:A9, A13, A21, A22, A23, A24.

Thrips tabaci (Onion thrips):

Sunflower leaf discs were placed on agar in a 24-well microtiter plateand sprayed with test solutions at an application rate of 200 ppm. Afterdrying, the leaf discs were infested with an aphid population of mixedages. After an incubation period of 7 days, samples were checked formortality. The following compounds gave at least 80% control of Thripstabaci: A13, A22.

The invention claimed is:
 1. A compound of formula (I)

wherein A¹, A² and A³ are independently C—R⁵, nitrogen, N—R⁶, oxygen orsulfur, provided that two of A¹, A² or A³ are C—R⁵ or nitrogen and thatone of A¹, A² or A³ is N—R⁶, oxygen or sulfur; A⁴ and A⁵ areindependently C—R⁵ or nitrogen; G¹ is oxygen or sulfur; R¹ is hydrogen,C₁-C₈alkyl, C₁-C₈alkylcarbonyl-, or C₁-C₈alkoxycarbonyl-; R² isC₁-C₈alkyl or C₁-C₈alkyl substituted by one to five R⁷, C₃-C₁₀cycloalkylor C₃-C₁₀cycloalkyl substituted by one to five R⁸, aryl-C₁-C₄alkylene-or aryl-C₁-C₄alkylene- wherein the aryl moiety is substituted by one tofive R⁹, heterocyclyl-C₁-C₄alkylene- or heterocyclyl-C₁-C₄alkylene-wherein the heterocyclyl moiety is substituted by one to five R⁹, arylor aryl substituted by one to five R⁹, heterocyclyl or heterocyclylsubstituted by one to five R⁹, C₁-C₈alkylaminocarbonyl-C₁-C₄ alkylene,C₁-C₈haloalkylaminocarbonyl-C₁-C₄ alkylene, orC₃-C₈cycloalkyl-aminocarbonyl-C₁-C₄ alkylene; R³ is C₁-C₈haloalkyl; R⁴is aryl or aryl substituted by one to five R¹⁰, or heteroaryl orheteroaryl substituted by one to five R¹⁰; each R⁵ is independentlyhydrogen, halogen, cyano, nitro, C₁-C₈alkyl, C₁-C₈haloalkyl,C₁-C₈alkoxy, C₁-C₈haloalkoxy, C₁-C₈alkylthio-, C₁-C₈haloalkylthio-,C₁-C₈alkylsulfinyl-, C₁-C₈haloalkylsulfinyl-, C₁-C₈alkylsulfonyl-, orC₁-C₈haloalkylsulfonyl-; each R⁶ is independently hydrogen orC₁-C₈alkyl; each R⁷ is independently halogen, cyano, nitro, hydroxy,C₁-C₈alkoxy, C₁-C₈haloalkoxy, mercapto, C₁-C₈alkylthio-,C₁-C₈haloalkylthio-; C₁-C₈alkylsulfinyl-, C₁-C₈haloalkylsulfinyl-,C₁-C₈alkylsulfonyl-, or C₁-C₈haloalkylsulfonyl-; each R⁸ isindependently halogen or C₁-C₈alkyl; each R⁹ and R¹⁰ is independentlyhalogen, cyano, nitro, C₁-C₈alkyl, C₁-C₈haloalkyl, C₂-C₈alkenyl,C₂-C₈haloalkenyl, C₂-C₈alkynyl, C₂-C₈haloalkynyl, hydroxy, C₁-C₈alkoxy,C₁-C₈haloalkoxy, mercapto, C₁-C₈alkylthio-, C₁-C₈haloalkylthio-,C₁-C₈alkylsulfinyl-, C₁-C₈haloalkylsulfinyl-, C₁-C₈alkylsulfonyl-,C₁-C₈haloalkylsulfonyl-, C₁-C₈alkylcarbonyl-, C₁-C₈alkoxycarbonyl-, arylor aryl substituted by one to five R¹¹, or heterocyclyl or heterocyclylsubstituted by one to five R¹¹; and each R¹¹ is independently halogen,cyano, nitro, C₁-C₄alkyl, C₁-C₄haloalkyl, C₁-C₄alkoxy, orC₁-C₄haloalkoxy; or a salt or N-oxide thereof; provided that -A¹-A²-A³-is not —O—(CR⁵)═N—, —S—(CR⁵)═N—, N═(CR⁵)—O— or —N═(CR⁵)—S— irrespectiveof the values for A⁴ and A⁵, and provided that -A¹-A²-A³- is not—(CR⁵)═(CR⁵)—O—, —O—(CR⁵)═(CR⁵)—, —(CR⁵)═(CR⁵)—S—, —S—(CR⁵)═(CR⁵)—,—(CR⁵)═(CR⁵)—(NR⁶)—, —(NR⁶)—(CR⁵)═(CR⁵)—, —(CR⁵)═N—(NR⁶)— and—(NR⁶)—N═(CR⁵)— when A⁴ and A⁵ are both C—R⁵.
 2. A compound according toclaim 1 wherein A¹ and A³ are nitrogen or N—R⁶ and A² is C—R⁵, N—R⁶,nitrogen or sulfur.
 3. A compound according to claim 1 wherein-A¹-A²-A³- is selected from ═N—S—N═, —N═C(R⁵)—N(R⁶)—, —N(R⁶)—C(R⁵)═N—,═N—N(R⁶)—N═, —N═N—N(R⁶)— and —N(R⁶)—N═N—.
 4. A compound according toclaim 1 wherein A⁴ and A⁵ are C—R⁵.
 5. A compound according to claim 1wherein G¹ is oxygen.
 6. A compound according to claim 1 wherein R¹ ishydrogen, methyl, ethyl, methylcarbonyl-, or methoxycarbonyl-.
 7. Acompound according to claim 1 wherein R² is C₁-C₈alkyl or C₁-C₈alkylsubstituted by one to five R⁷, C₃-C₁₀cycloalkyl or C₃-C₁₀cycloalkylsubstituted by one to five R⁸, phenyl-C₁-C₄alkylene- orphenyl-C₁-C₄alkylene- wherein the phenyl moiety is substituted by one tofour R⁹, pyridyl-C₁-C₄alkylene- or pyridyl-C₁-C₄alkylene- wherein thepyridyl moiety is substituted by one to four R⁹, oxetanyl or oxetanylsubstituted by one to five R⁹, thietanyl or thietanyl substituted by oneto five R⁹, oxo-thietanyl or oxo-thietanyl substituted by one to fiveR⁹, or dioxo-thietanyl or dioxo-thietanyl substituted by one to five R⁹.8. A compound according to claim 1 wherein R³ is chlorodifluoromethyl ortrifluoromethyl.
 9. A compound according to claim 1 wherein R⁴ is arylor aryl substituted by one to five R¹⁰.
 10. A compound according toclaim 1 wherein A¹ and A³ are nitrogen or N—R⁶ and A² is C—R⁵, N—R⁶,nitrogen or sulfur, provided that two of A¹, A² or A³ are C—R⁵ ornitrogen and that one of A¹, A² or A³ is N—R⁶ or sulfur; A⁴ and A⁵ areCH; G¹ is oxygen; R¹ is hydrogen, methyl or ethyl; R² is C₁-C₈alkyl orC₁-C₈alkyl substituted by one to five R⁷, C₃-C₁₀cycloalkyl or C₃-C₁₀cycloalkyl substituted by one to five R⁸, phenyl-C₁-C₄alkylene- orphenyl-C₁-C₄alkylene- wherein the phenyl moiety is substituted by one tofive R⁹, pyridyl-C₁-C₄alkylene- or pyridyl-C₁-C₄alkylene- wherein thepyridyl moiety is substituted by one to four R⁹,imidazolyl-C₁-C₄alkylene or imidazolyl- C₁-C₄alkylene wherein theimidazolyl moiety is substituted by one to five R⁹, oxetanyl or oxetanylsubstituted by one to five R⁹, thietanyl or thietanyl substituted by oneto five R⁹, oxo-thietanyl or oxo-thietanyl substituted by one to fiveR⁹, dioxo-thietanyl or dioxo-thietanyl substituted by one to five R⁹,C₁-C₈alkylaminocarbonyl-C₁-C₄ alkylene,C₁-C₈haloalkylaminocarbonyl-C₁-C₄ alkylene, orC₃-C₈cycloalkyl-aminocarbonyl-C₁-C₄ alkylene; R³ is chlorodifluoromethylor trifluoromethyl; R⁴ is 3,5-dibromo-phenyl-, 3,5-dichloro-phenyl-,3,4-dichloro-phenyl-, 4-bromo-3,5-dichloro-phenyl or3,4,5-trichloro-phenyl-; R⁵ is independently hydrogen, bromo, chloro,fluoro, cyano, nitro, methyl, ethyl, trifluoromethyl, methoxy,difluoromethoxy, or trifluoromethoxy; R⁶ is hydrogen, methyl or ethyl;each R⁷ is independently bromo, chloro, fluoro, methyl, methoxy, ormethylthio; each R⁸ is methyl; each R⁹ is independently bromo, chloro,fluoro, cyano, nitro, methyl, ethyl, trifluoromethyl, methoxy,difluoromethoxy, or trifluoromethoxy.
 11. A compound according to claim1 wherein -A¹-A²-A³- is selected from ═N—S—N═, —N═C(R⁵)—N(R⁶)—,—N(R⁶)—C(R⁵)═N—, ═N—N(R⁶)—N═, —N═N—N(R⁶)— and —N(R⁶)—N═N—; A⁴ and A⁵ areCH; G¹ is oxygen; R¹ is hydrogen; R² is C₁-C₈alkyl or C₁-C₈alkylsubstituted by one to five R⁷, C₃-C₁₀cycloalkyl or C₃-C₁₀ cycloalkylsubstituted by one or two methyl groups, phenyl-C₁-C₄alkylene- orphenyl-C₁-C₄alkylene- wherein the phenyl moiety is substituted by one tofive R⁹, pyridyl-C₁-C₄alkylene- or pyridyl-C₁-C₄alkylene- wherein thepyridyl moiety is substituted by one to four R⁹,imidazolyl-C₁-C₄alkylene or imidazolyl-C₁-C₄alkylene wherein theimidazolyl moiety is substituted by one to five R⁹, oxetanyl or oxetanylsubstituted by one to five R⁹, thietanyl or thietanyl substituted by oneto five R⁹, oxo-thietanyl or oxo-thietanyl substituted by one to fiveR⁹, dioxo-thietanyl or dioxo-thietanyl substituted by one to five R⁹; R³is trifluoromethyl; R⁴ is 3,5-dichloro-phenyl; R⁵ is hydrogen or methyl;R⁶ is hydrogen or methyl; each R⁷ is independently bromo, chloro,fluoro, methoxy, or methylthio; each R⁹ is independently bromo, chloro,fluoro, nitro, or methyl.
 12. A method of combating and/or controllinginsects, acarines, nematodes or molluscs which comprises applying to apest, to a locus of a pest, or to a plant susceptible to attack by apest an insecticidally, acaricidally, nematicidally or molluscicidallyeffective amount of a compound of formula (I) as defined in claim
 1. 13.An insecticidal, acaricidal, nematicidal or molluscicidal compositioncomprising an insecticidally, acaricidally, nematicidally ormolluscicidally effective amount of a compound of formula (I) as definedin claim
 1. 14. An insecticidal, acaricidal, nematicidal ormolluscicidal composition according to claim 13 comprising an additionalcompound having biological activity.
 15. A compound of formula (A)

wherein A¹, A² and A³ are independently C—R⁵, nitrogen, N—R⁶, oxygen orsulfur, provided that two of A¹, A² or A³ are C—R⁵ or nitrogen and thatone of A¹, A² or A³ is N—R⁶, oxygen or sulfur; A⁴ and A⁵ areindependently C—R⁵ or nitrogen; G¹ is oxygen or sulfur; R¹ is hydrogen,C₁-C₈alkyl, C₁-C₈alkylcarbonyl-, or C₁-C₈alkoxycarbonyl-; R² iscyclobutyl or cyclobutyl substituted by one to five R⁸, oxetanyl oroxetanyl substituted by one to five R⁹, thietanyl or thietanylsubstituted by one to five R⁹, oxo-thietanyl or oxo-thietanylsubstituted by one to five R⁹, or dioxo-thietanyl or dioxo-thietanylsubstituted by one to five R⁹; R³ is C₁-C₈haloalkyl; R⁴ is aryl or arylsubstituted by one to five R¹⁰, or heteroaryl or heteroaryl substitutedby one to five R¹⁰; each R⁵ is independently hydrogen, halogen, cyano,nitro, C₁-C₈alkyl, C₁-C₈haloalkyl, C₁-C₈alkoxy, C₁-C₈haloalkoxy,C₁-C₈alkylthio-, C₁-C₈haloalkylthio-, C₁-C₈alkylsulfinyl-,C₁-C₈haloalkylsulfinyl-, C₁-C₈alkylsulfonyl-, orC₁-C₈haloalkylsulfonyl-; each R⁶ is independently hydrogen orC₁-C₈alkyl; each R⁸ is independently halogen or C₁-C₈alkyl; each R⁹ andR¹⁰ is independently halogen, cyano, nitro, C₁-C₈alkyl, C₁-C₈haloalkyl,C₂-C₈alkenyl, C₂-C₈haloalkenyl, C₂-C₈alkynyl, C₂-C₈haloalkynyl, hydroxy,C₁-C₈alkoxy, C₁-C₈haloalkoxy, mercapto, C₁-C₈alkylthio-,C₁-C₈haloalkylthio-, C₁-C₈alkylsulfinyl-, C₁-C₈haloalkylsulfinyl-,C₁-C₈alkylsulfonyl-, C₁-C₈haloalkylsulfonyl-, C₁-C₈alkylcarbonyl-,C₁-C₈alkoxycarbonyl-, aryl or aryl substituted by one to five R¹¹, orheterocyclyl or heterocyclyl substituted by one to five R¹¹; and eachR¹¹ is independently halogen, cyano, nitro, C₁-C₄alkyl, C₁-C₄haloalkyl,C₁-C₄alkoxy, or C₁-C₄haloalkoxy; or a salt or N-oxide thereof.
 16. Acompound according to claim 15, wherein -A¹-A²-A³- is selected from═N—S—N═, —S—N═N—, —N═N—S—, ═N—N(R⁶)—N═, —N═N—N(R⁶)—, —N(R⁶)—N═N—,—C(R⁵)═N—N(R⁶)—, —N(R⁶)—N═C(R⁵)—, —N═C(R⁵)—N(R⁶)—, —N(R⁶)—C(R⁵)═N—,—N═C(R⁵)—O— and —O—C(R⁵)═N—; A⁴ and A⁵ are independently CH or nitrogen;G¹ is oxygen; R¹ is hydrogen, methyl, ethyl, methylcarbonyl-, ormethoxycarbonyl-; R² is cyclobutyl or cyclobutyl substituted by one tofive R⁸, oxetanyl or oxetanyl substituted by one to five R⁹, thietanylor thietanyl substituted by one to five R⁹, oxo-thietanyl oroxo-thietanyl substituted by one to five R⁹, or dioxo-thietanyl ordioxo-thietanyl substituted by one to five R⁹; R³ is C₁-C₈haloalkyl; R⁴is phenyl substituted by two to three R¹⁰; R⁵ is hydrogen, bromo,chloro, fluoro, cyano, nitro, methyl, ethyl, trifluoromethyl, methoxy,difluoromethoxy, or trifluoromethoxy; R⁶ is hydrogen or C₁-C₈alkyl; eachR⁸ is independently chloro, fluoro or methyl; each R⁹ is independentlyhalogen, cyano, nitro, C₁-C₈alkyl, C₁-C₈haloalkyl, C₁-C₈alkoxy,C₁-C₈haloalkoxy; each R¹⁰ is independently halogen, C₁-C₈alkoxy,C₁-C₈haloalkoxy, C₁-C₈alkylthio-, or C₁-C₈haloalkylthio-.